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Home , Biological membrane

Cell Features Introductory article

Philip L Yeagle, Rutgers University, Newark, New Jersey, USA Article Contents . Introduction . Structure

. Function of

. Membrane Fusion

. Mammalian Cell Membranes

. Other Biological Membranes

Online posting date: 15th December 2009

The membranes of living cells support much of the func- intracellular transport, as well as support a host of other tionality of biology. From the subcellular level of organ- cellular activities. In eukaryotic cells, all the internal elles to the supercellular level of cell–cell interactions, are defined by membranes. Consistent with this membranes provide the structures necessary for bio- focus of cellular activity on cell membranes, it is estimated that nearly half of all expressed are integral logical function and organization. Many of those struc- membrane proteins, and many more are associated with tural and functional features are common among cell membranes. See also: Cell Structure membranes in bacteria, eukaryotic cells and viruses. The An appreciation of the many facets of bilayer provides the fundamental architecture and structure and function can be gained by initially con- some of the properties common to all biological mem- sidering separately the two major components of cell branes. Membrane proteins confer a myriad of specific membrane structure: the and membrane functions expressed by cell membranes. Plasma mem- proteins. branes determine the boundary of the cell and many of the interactions of the cell with its environment. Intra- cellular membranes compartmentalize cells into different Structure functional units with differing internal compositions. The composition of the compartments is maintained by Lipid bilayer essential transport functions in concert with permeability control. is supported by membranes. The architecture of biological membranes is designed on Membrane fusion provides a mechanism for intracellular the structure of the lipid bilayer. All biological membranes contain the bilayer structure. The bilayer structure is based vesicular transport and enveloped virus entry into cells. on the chemical structure of the lipid constituents and the hydrophobic effect. See also: Lipid Bilayers Some properties of cell membranes are derived directly from lipid bilayers. These properties include a (nearly) two- dimensional structure, ordered fluid properties, limited Introduction permeability, ability to confer charge on membrane sur- faces, ability to regulate function through individual lipid Membranes compartmentalize cellular function, control species in the bilayer and asymmetry. cell–cell recognition, transduce extracellular signals to regulate internal cellular activity, synthesize adenosine Two-dimensional structure of lipid bilayers triphosphate (ATP), the common currency of cellular Most of the of biological membranes have an energy, create pathways for controlled internal transport of amphipathic chemical structure. Most lipids consist of a materials around the cell, enable and regulate all transport polar, hydrophilic headgroup (often with charged con- of material between the inside and the outside of cells, stituents) and hydrophobic hydrocarbon chains. The connect and disconnect membranes during cell entry and hydrophobic effect drives the formation of lipid bilayers in the aqueous environment, whether as pure lipids in an aqueous environment or as lipids in a biological membrane ELS subject area: Cell Biology in living cells. The hydrophobic hydrocarbon chains of the membrane lipids must be sequestered from the aqueous How to cite: environment, leaving the polar headgroups to interact with Yeagle, Philip L (December 2009) Cell Membrane Features. In: Encyclo- the water. This leads to the formation of the lipid bilayer, as pedia of Life Sciences (ELS). John Wiley & Sons, Ltd: Chichester. represented schematically in Figure 1. Lipid bilayers repre- DOI: 10.1002/9780470015902.a0001261.pub2 sent nearly a two-dimensional world. While membranes

ENCYCLOPEDIA OF LIFE SCIENCES & 2009, John Wiley & Sons, Ltd. www.els.net 1 Cell Membrane Features

Water Limited permeability The lipid bilayer is relatively impermeable to solutes and thus forms an effective barrier to movement of solutes from one side of a cell membrane to another. Since the interior of the lipid bilayer is hydrophobic, polar compounds are largely excluded from the interior and thus the trans- membrane transit by polar molecules is inhibited. Imper- meability, a fundamental characteristic of lipid bilayers, imparts to cell membranes one of the properties crucial to cell survival, the compartmentalization of cell function. Since solutes cannot readily pass through the lipid bilayer, solutes must get into and out of a cell through transport functions catalysed and regulated by membrane proteins. Water Thus, solute movements between cellular compartments Figure 1 Schematic representation of a lipid bilayer. The circles represent and into and out of the cell can be tightly controlled by the polar headgroups of the lipids, and the lines connected to the circle membrane proteins in cell membranes. Charge and represent the hydrophobic hydrocarbon chains of the lipids. These enzymatic regulation by the lipid bilayer. amphipathic molecules are dual nature: one end is hydrophilic and the other end is hydrophobic. They organize so as to limit the exposure of the The lipid compositions of biological membranes are hydrophobic portions to the aqueous phase that is found on both sides of the complex. Many different hydrocarbon chains can be used membrane. and many different headgroups can be used to construct membrane lipids. Consequently, several thousand indi- vidual species of lipids are known to exist in nature. This complexity is thought to regulate the function of mem- extend in two dimensions, the third dimension is limited, brane proteins and other membrane properties. Specific defined by the length of two lipid molecules. Therefore the lipid– interactions in which lipids with specific lipid bilayer has some characteristics of a huge but very thin structures bind to particular membrane enzymes modulate macromolecule with many ‘subunits’ (lipids) because it is enzyme function. Lipids with charged headgroups confer an extended structure that can cover a whole cell, yet the local charge on the membrane surface. The structure of the ‘subunits’ are not covalently connected. See also: Hydro- lipid bilayer stabilizes membrane proteins against phobic Effect; Lipids; Membrane Lipid Biosynthesis; denaturation. Water: Structure and Properties is an essential lipid in mammalian cells that exhibits many of these functions. Cholesterol is found Ordered fluid predominantly in the plasma membrane of mammalian cells. Yeast have ergosterol as their essential sterol in their The lipid bilayer of cellular membranes allows lateral plasma membrane. Plant cells have yet different sterols, movement, or diffusion, of lipids in the plane of the mem- such as sitosterol. The specificity of sterol is likely due to the brane. However, movement in and out of the plane of the interaction between specific sterol structures and particular membrane is limited by the hydrophobic effect and the membrane proteins in these cells to regulate crucial cellular chemical structure of the membrane lipids (i.e. the lipids are functions. Cholesterol also orders (see section on Ordered not soluble in water). This limitation imposes some order fluid) the lipid hydrocarbon chains in the bilayer and ren- on the system. Additional order at the submolecular level is ders bilayers even less permeable to solutes than in the imposed by the side-by-side arrangement of the lipids in the absence of cholesterol. Some bacteria have sterols and bilayer. The lipid hydrocarbon chains exhibit some intra- others do not require this lipid for growth. Enveloped molecular order that is manifest in limitations on the viruses (viruses with a membrane around the nucleocapsid) rotation around carbon–carbon bonds in the hydrocarbon will have sterols characteristic of the cell in which they chains of the lipids. There is greater conformational flexi- propagate and some require cholesterol for infection. bility of the hydrocarbon chain in the centre of the bilayer Although much remains to be understood about how these than in the region near the lipid headgroups. effects are achieved, lipids clearly play both fundamental Lateral diffusion of the proteins also occurs and can be and specific roles in biological membrane structure and important to membrane function, allowing some proteins function. See also: Bacterial Cytoplasmic Membrane; to properly associate for expression of their activity. In Cholesterol, Steroid and Isoprenoid Biosynthesis; Viral some cases, the lateral movement of membrane com- Capsids and Envelopes: Structure and Function ponents is restricted. This can lead to patches of different composition in the plane of the membrane (rafts). Extreme constriction occurs when membrane proteins are anchored Membrane proteins to a membrane skeleton, a part of the cell cytoskeleton lying immediately under the plasma membrane and con- Membrane proteins and lipid bilayers are the major com- nected to the latter. See also: Membrane Dynamics ponents of cell membranes. Membrane proteins impart

2 ENCYCLOPEDIA OF LIFE SCIENCES & 2009, John Wiley & Sons, Ltd. www.els.net Cell Membrane Features many functions to biological membranes and thus to the cells of which they are a part. However, membrane proteins exhibit distinct structural differences from water-soluble proteins because of their membrane location.

Membrane protein structure Proteins are linear polymers of amino acids. Some of the amino acids are hydrophobic and some are hydrophilic. The hydrophobic effect controls protein structure as it controls bilayer structure. The hydrophobic effect repre- sents the high cost in free energy (mostly entropy) of an encounter between water and compounds such as hydro- carbons that cannot participate (through hydrogen bond, Figure 2 Schematic representation of the incorporation of a for example) in the structure of water. In such cases, water transmembrane protein into a lipid bilayer. The cylinders represent hydro- molecules must organize (involving unfavourable entropy phobic transmembrane a helices, the dark lines are loops of the polypeptide change) in dynamic arrays, or ‘cages’, around such com- chain that connect the helices, and the lipids are represented as in Figure 1. pounds. The energy cost of forming these ‘cages’ is so high that hydrocarbons are excluded from water to a very high degree. See also: Hydrophobic Effect; Water: Structure and include proteins that have hydrophobic lipid covalently Properties attached. Associated proteins are peripheral membrane The structure of water-soluble proteins is conceptually proteins that are bound to integral membrane proteins, and simple in this regard. After synthesis, when these linear skeletal membrane proteins form a network underlying the polymers of amino acids fold into functional proteins, the plasma membrane of a cell. hydrophobic amino acids must be sequestered largely in the Integral membrane proteins can be further classified as interior of the protein so as not to encounter water, while transmembrane proteins or anchored proteins (Figure 3). the hydrophilic amino acids largely coat the surface of Transmembrane proteins completely traverse the lipid the protein, interacting with the water. See also: Amino bilayer and expose some of their mass on both sides of the Acid Side-chain Hydrophobicity; Proteins: Fundamental membrane. An example of such a protein is the - Chemical Properties coupled receptor that transduces signals from one side of Membrane proteins that bury a portion of their mass in the membrane to the other. The functionality requires that the lipid bilayer must satisfy a different topology. Linear some of the protein be exposed on both sides of the mem- sequences of hydrophobic amino acids in the membrane brane. Anchored membrane proteins have part of their protein are used to transit the hydrophobic interior of the mass buried within the hydrophobic part of the lipid bilayer. For proteins that traverse the bilayer, called trans- bilayer, but with structures that do not completely traverse membrane proteins, a linear sequence of 19–23 hydrophobic the membrane. An example can be found in the lipid- amino acids is utilized to cross the bilayer. When 19–23 anchored proteins like Thy1 that resemble soluble proteins amino acids form a helix (the amino acid polymer coils into a but are covalently linked to an amphipathic membrane helical structure with a defined geometry and is termed lipid that anchors the protein into the outer leaflet of the secondary structure), the length of the helix approximates plasma membrane. Alternatively, in some cases the lipid is the thickness of the hydrophobic interior of the lipid bilayer. a fatty acid or isoprenoid, and the hydrophobic moiety can For most transmembrane proteins in cell membranes, control whether the protein is membrane bound or not hydrophobic a-helices form the transmembrane domain of through incorporation into the cytoplasm-facing leaflet of the protein. Figure 2 shows a schematic representation of a cell membranes. See also: G Protein-coupled Receptors transmembrane protein with a bundle of hydrophobic Peripheral membrane proteins are associated with cell helices. The transmembrane regions of some bacterial membranes, but do not significantly penetrate the hydro- membrane proteins are formed from b sheets, another type phobic interior of the lipid bilayer. The general aspects of of secondary structure. Such b sheet structures can be the three-dimensional structure of peripheral membrane formed into a channel lined with polar amino acids and proteins resemble those of water-soluble proteins. Per- suitable for solutes to traverse the membrane. See also: ipheral membrane proteins can be classified as associated Hydrophobicity Plots; Membrane Proteins; Protein Sec- membrane proteins or as membrane skeleton (Figure 3). ondary Structures: Prediction Associated membrane proteins bind to integral membrane Membrane proteins can be classified as integral mem- proteins (or to the surface of the lipid bilayer through brane proteins, of which the transmembrane protein is an electrostatic interactions with lipid headgroups). They may example, and peripheral membrane proteins. These classes form part of a functioning complex with the integral of membrane proteins can be subdivided further as indi- . An example is cytochrome c, which cated in Figure 3. Anchored membrane proteins insert a binds to cytochrome c oxidase (an integral membrane hydrophobic portion into one leaflet of the bilayer and protein in the inner mitochondrial membrane) to donate an

ENCYCLOPEDIA OF LIFE SCIENCES & 2009, John Wiley & Sons, Ltd. www.els.net 3 Cell Membrane Features

Integral compartments to have different compositions, which can Associated be critical to cell function. For example, the outside of mammalian cells is relatively high in sodium while the Anchored cytoplasm is relatively low in sodium. The plasma mem- brane keeps the two compartments separate; this is critical, for example, to maintaining ion gradients required for action potentials. Another example can be seen in the sequestration of degradative enzymes in the lysosome by the lysosomal membrane. ATP synthesis in the mito- Transmembrane chondria depends upon a differential in proton concen- Anchored Associated tration inside and outside the mitochondrial lumen. See also: Action Potential: Ionic Mechanisms; Lysosomal Skeletal Degradation of Proteins; Membrane Potential Peripheral Figure 3 Schematic representation of the classes of membrane proteins. Transport The darker shaded regions are the hydrophobic portions of these membrane proteins and the clear horizontal box represents the lipid bilayer. The The relative impermeability of the lipid bilayer permits cel- transmembrane proteins are exposed on both sides of the membrane; anchored membrane proteins penetrate only one half of the lipid bilayer; lular compartments separated by membranes to have sig- associated membrane proteins bind to transmembrane proteins as part of a nificantly different compositions. For example, the cytoplasm complex; and skeletal membrane proteins form a network underneath the of the cell is depleted in calcium relative to the lumen of the plasma membrane that can give shape to a cell. endoplasmic reticulum and relative to the outside of the cell. The cytoplasm of a mammalian cell has a significantly lower electron as part of the electron transport chain supporting sodium concentration than the outside of the cell. How are the synthesis of ATP in the inner mitochondrial membrane. these differences in composition established and maintained? Proteins can also form a skeleton lining the inside of the The answer lies in the transport function of biological mem- plasma membrane of cells. These proteins of the membrane branes. Membranes tightly regulate the composition of the skeleton bind in turn to integral membrane proteins or to compartments they enclose by controlling the access to these associated membrane proteins that are themselves bound compartments for various solutes and by ‘pumping’ solutes to integral membrane proteins. An example is spectrin, into or out of compartments. Transport across membranes which forms, in part, the membrane skeleton lining the can be divided into two kinds: passive and active. See also: inside of the plasma membrane of the erythrocyte. Spectrin Intracellular Transport; Ion Transport Across Nonexcitable binds to ankyrin, an associated protein, which in turn binds Membranes to band 3, a transmembrane protein (which is involved in anion transport). These proteins can regulate cell shape through phosphorylation, subject to the metabolic state of Passive transport only achieves net movement of solutes the cell. Skeletal proteins can also influence the behaviour across a membrane when the movement is from a higher of integral membrane proteins by restricting their lateral concentration to a lower concentration. Thus, passive c diffusion. See also: Cytochrome Oxidase; Erythrocytes; transport leads toward chemical equilibrium. Passive Erythrocyte Membrane Disorders; Mitochondria: Struc- transport cannot move solutes across a membrane from a ture and Role in Respiration lower concentration to a higher concentration. Passive transport can be simple diffusion of small mol- ecules across a bilayer. Since lipid bilayers are relatively Function of Cell Membranes impermeable to any solutes, this normally occurs very slowly and is observed only when the solutes are small Collectively, the membrane proteins, both integral and molecules. Because the interior of the lipid bilayer is peripheral, provide much of the functionality to cell hydrophobic, it is thermodynamically unfavourable for membranes. Cell membranes, in turn, make possible many water-soluble solutes to enter the bilayer interior, and thus of the functions exhibited by living cells. These include passage of water-soluble solutes through the membrane is compartmentalization, transport, signal transduction and characterized by a relatively low probability. For example, membrane fusion. glucose can diffuse only slowly across a lipid bilayer. The larger molecule of sucrose will diffuse so much more slowly Compartmentalization that lipid bilayers are considered to be impermeable to sucrose. Lipid bilayers are also relatively impermeable Because of the regulated permeability of cell membranes, to charged solutes, like sodium ions, because of the cell membranes separate compartments within the cell unfavourable free energy cost of introducing a charged and separate the inside of the cell from the outside of the species into the bilayer interior. On the other hand, small cell. Compartmentalization allows individual intracellular molecules with some hydrophobic character, like ethanol,

4 ENCYCLOPEDIA OF LIFE SCIENCES & 2009, John Wiley & Sons, Ltd. www.els.net Cell Membrane Features are more freely permeable. See also: Cell Biophysics; Signal transduction Cellular Thermodynamics Passive transport in biological membranes is more Regulation of biological function at the cellular level is importantly manifest as facilitated diffusion. To overcome essential to normal function of any organism. Regulation the thermodynamic barrier encountered by a polar solute may be intracellular or may occur in response to an in crossing a lipid bilayer, facilitated diffusion uses integral extracellular signal. Because of the barrier function membrane proteins to create an alternative pathway across exhibited by the plasma membrane, special mechanisms are a membrane. One way in which this can be achieved is for required to communicate changes in the extracellular the protein to exhibit as part of its three-dimensional environment to the interior of the cell. Regulation of cell structure a polar channel suitable, or even specific, for the behaviour by hormones or other signals from the outside of solute of interest. One way to build a channel is to form one the cell is achieved through the process of signal trans- in which the transmembrane helices of the membrane duction mediated by receptors (transmembrane proteins) protein contain polar amino acids that face the interior of in the plasma membrane of the cell. Binding of a ligand to the channel, thus allowing polar solutes to transverse the the extracellular face of a receptor can alter its conform- membrane in a polar environment. The glucose transporter ation, which can be transmitted as a conformation change of mammalian cells is an example of a transmembrane to the intracellular face of the receptor protein. Such a protein that provides a pathway for facilitated diffusion of change in conformation acts as a signal inside the cell. glucose across the plasma membrane. The potassium Either some function is expressed directly by this con- channel protein creates a channel lined with polar car- formational change or a cascade of intracellular events is bonyls suitable for potassium ions to sequentially bind (to initiated, often mediated by a series of cytoplasmic a series of sites) and pass through the membrane. In each proteins. case, the solute transported moves down a concentration An example of the former can be found in the acetyl- gradient, to a compartment of lower concentration. choline receptor. Binding of acetylcholine (from the presynaptic membrane) to the external part of this trans- membrane protein induces a conformational change. Opening of a sodium channel, results. Passive diffusion of Active transport is distinguished from passive transport by sodium ions across the postsynaptic membrane com- the utilization of cellular energy to support the transport of mences and changes the transmembrane electrical poten- solutes across a membrane, often against a concentration tial in the membrane. gradient, or from a compartment of lower concentration to a An example of the receptor-initiated cascade of intra- compartment of higher concentration. Cellular energy in the cellular events is the response of a G protein–coupled form of ATP hydrolysis is often used as the energy source receptor such as the visual pigment rhodopsin in the retinal for active transport. For example, the transport of calcium rod cell. A photon of light is absorbed by retinal, which into the lumen of the endoplasmic reticulum, where the undergoes a photoisomerization from 11-cis to all-trans concentration is nearly three orders of magnitude higher, retinal and induces a conformational change in this trans- requires the energy of ATP hydrolysis. The Ca2+ ATPase is membrane protein. The cytoplasmic face of the receptor is an integral membrane protein of the endoplasmic reticulum then altered to enable the binding and activation of the G membrane that couples the hydrolysis of ATP to the trans- protein, which, in turn, through its a subunit, activates the port of calcium up a concentration gradient. The extent of target enzyme phosphodiesterase, ultimately resulting in a the achievable calcium gradient is a function of the energy reduction in cyclic GMP that closes plasma membrane extractable from the coupled ATP hydrolysis. See also: sodium channels and causes a hyperpolarization across the Adenosine Triphosphate; : Ion-motive; Ion Motive plasma membrane. The latter becomes an electrical signal ATPases: P-type ATPases; Ion Transport Across Nonexci- interpretable by the brain. See also: Acetylcholine; Regu- table Membranes latory Cascade; Rhodopsin; Signal Transduction: Over- Another form of energy that can be used for transport of view; Transmembrane Signalling solutes against a concentration gradient across a cell membrane is the energy inherent in a concentration gra- dient. Thus the flow of solutes down a concentration gra- Membrane Fusion dient can be utilized to provide energy for the transport of another solute against its concentration gradient. An Membrane fusion is a process that fuses two membranes example can be found in glucose transport in the intestine. into one, or the reverse of that process (fission). An The plasma membrane of the intestinal mucosal cells important biological model is the fusion of an enveloped contains a protein that permits the coupled flow of sodium virus (a virus surrounded by a membrane) with the plasma ions from the outside of the cell into the cytoplasm (and membrane of a cell. Another example is found in intracel- thus down a concentration gradient) with the simultaneous lular transport when vesicles pinch off (the reverse of influx of glucose against its concentration gradient. This is fusion) from the endoplasmic reticulum and fuse with the also called a symport. In the case where the two transported trans Golgi. This is a process that, at least transiently, solutes flow in opposite directions, it is called an antiport. requires the destabilization of the lipid bilayer of the

ENCYCLOPEDIA OF LIFE SCIENCES & 2009, John Wiley & Sons, Ltd. www.els.net 5 Cell Membrane Features involved membranes such that the components of the two an intracellular second messenger. This cascade of events membranes, after close approach, can partially mix and leads to a significant change in intracellular . form a new, fused membrane. Specialized transmembrane See also: Adrenergic Receptors fusion proteins are required to facilitate this membrane Receptor-mediated is another function of fusion process. the plasma membrane. Some receptors, upon binding their ligand, cluster into coated pits, specialized regions of the plasma membrane coated on the cytoplasmic face with a Mammalian Cell Membranes protein called . Clathrin can mediate the formation of a vesicle from that portion of the plasma membrane that Plasma membrane separates from the plasma membrane and becomes an intracellular vesicle. This process will take extracellular The plasma membrane of the mammalian cell serves the material into the cell, such as the ligated receptor. See also: primary compartmentalization function for the cell, Clathrin-coated Vesicles and Receptor-mediated Endocy- demarcating the boundary between the cytoplasm and the tosis; Clathrin-coated Vesicles: Methods for Preparation exterior of the cell. This membrane contains both lipids The surface of mammalian cells is covered with complex and membrane proteins, in nearly equal mass. Since the carbohydrate called the glycocalyx. Some of this carbo- plasma membrane is composed of a lipid bilayer, the plas- hydrate is provided by and of ma membrane is sealed to the passage of solutes, except the plasma membrane. The glycocalyx may provide a through defined transport systems. Both active and passive protective coat to the cell, but these carbohydrate struc- transport systems are present in the plasma membrane. tures also form the basis of some cell recognition systems. These transport systems either maintain or utilize the dif- For example, blood type is determined in part by plasma ferences in solute composition on both sides of the mem- membrane glycoproteins on the surface of human eryth- brane for function. For example, permeabilities of sodium rocytes, as is cell adhesion in blood clotting, and sperm–egg and potassium are controlled to maintain a transmem- interactions. The cell coat of carbohydrate interacts with brane electrical potential. Sudden changes in permeability external matrix and is involved in cell motility. See also: through the opening of a sodium channel, for example, can Blood Clotting: General Pathway; Cell Surface Glycocon- lead to the initiation of an action potential. The sodium jugates; Extracellular Matrix; Glycoproteins; Sperm–Egg gradient is maintained by the Na+/K+ ATPase, an enzyme Interactions: Sperm–Egg Binding in Mammals in the plasma membrane that transports sodium out of the The plasma membrane of many cells is lined on the inside cell and potassium into the cell, against both concentration with a network of proteins forming a membrane skeleton gradients by linking the transport to the hydrolysis of ATP. associated with the cytoplasmic face of the plasma mem- This particular transport system is so important that it is brane. In the erythrocyte, this membrane skeleton gives the the single greatest consumer of cellular ATP in many cells. cell its characteristic shape. Membrane skeletons can con- See also: Adenosine Triphosphate; Cell Membranes: nect with cytoskeletal networks. These networks in turn Intracellular pH and Electrochemical Potential; Cell can connect through the plasma membrane to other cells Structure; Plasma Membranes: Methods for Preparation such as at desmosomes. See also: Cytoskeleton ATP can be made through glycolysis, which utilizes, in These few examples serve to illustrate the complex part, glucose transported across the plasma membrane by a functionality of the plasma membrane of mammalian cells. passive transport system. The glucose transporter of many cells is a transmembrane protein that forms a channel Endoplasmic reticulum specific for the passage of glucose from the blood to the cytoplasm of the cell where it can be metabolized by the The endoplasmic reticulum is an intracellular enzymes of the glycolytic pathway. This transporter is bound by membranes with a mass ratio of lipid to protein under the control of the insulin receptor. Activation of the similar to that in the plasma membrane. The endoplasmic insulin receptor, a transmembrane protein of the plasma reticulum functions as a factory for the biosynthesis of membrane, by binding of insulin on the receptor face membrane lipids and membrane proteins, as well as pro- outside the cell can lead to the recruitment of additional teins to be secreted. The early steps of synthesis of the lipids glucose transporters to the plasma membrane. The increase utilize soluble enzymes, but the later steps all use mem- in number of transporters increases the flux of glucose into brane-bound enzymes because of the hydrophobic nature the cell. See also: Glycolysis Regulation; Glycolytic of the lipid. Integral membrane proteins are made on the Pathway endoplasmic reticulum in a concerted process involving Receptors are located in the plasma membrane. The membrane-bound ribosomes. Synthesis of the integral b-adrenergic receptor, another transmembrane protein in membrane protein proceeds in concert with folding and the plasma membrane of some cells, upon binding its li- insertion of the hydrophobic portions of the membrane gand, adrenaline, will change its conformation and activate proteins into the protein. Proteins to be secreted are also the corresponding G protein in the cytoplasm. This G synthesized on ribosomes bound to the endoplasmic protein, in turn, activates adenylate cyclase, increasing the reticulum membrane, and the synthesis process occurs in production of cyclic adenosine monophosphate (cAMP), concert with the transport of the protein into the lumen of

6 ENCYCLOPEDIA OF LIFE SCIENCES & 2009, John Wiley & Sons, Ltd. www.els.net Cell Membrane Features this organelle. Early stages of protein glycosylation also Targeting: Methods; Plant ; Protein occur in the endoplasmic reticulum, mostly on asparagines Translocation Across Membranes (N-linked glycosylation) in (not in pro- karyotes). Core carbohydrate structures are synthesized in Endosomes the endoplasmic reticulum membrane on dolichol, a hydrophobic isoprenoid, and are transferred to the newly A specialized set of intracellular organelles receives synthesized protein. This synthesis of precursor carbo- materials taken up by the cell through receptor-mediated hydrate structures undergoes some processing and further endocytosis. Endosomes are defined by a membrane, based maturation eventually in the Golgi. See also: Plant on a lipid bilayer containing many membrane proteins. Endoplasmic Reticulum; Protein Import into Endoplasmic After fusion of coated vesicles with these endosomes, Reticulum: Methods; Proteins: Postsynthetic Modification sorting of components of the coated vesicles can occur. – Function and Physical Analysis Sometimes the receptor is recycled to the plasma mem- A specialized machinery for intracellular transport ori- brane, while the ligands may be used within the cell. Some ginates in the endoplasmic reticulum. Transport of newly components are shunted to the lysosome for degradation. synthesized membrane components, and proteins to be See also: Endocytic Organelles: Methods for Preparation secreted, to the Golgi and other intracellular targets is achieved by membrane-bound vesicles. These vesicles Nuclear membrane pinch off from the endoplasmic reticulum in a regulated The nuclear envelope is a double membrane, based on the process that sorts proteins to be transported, from native lipid bilayer and each membrane contains many membrane endoplasmic reticulum proteins involved in protein and proteins. The nuclear membrane system surrounds the lipid synthesis, which are not transported. The process of nucleus. The inner membrane is continuous with, but vesicular transport is energy-dependent, utilizes a complex compositionally distinct from, the outer nuclear mem- protein machinery and requires the processes of membrane brane, which is connected to the endoplasmic reticulum. fusion. Membrane fusion processes include fusion of two The nuclear membrane is involved in regulation of gene membranes to become one membrane and fission of one expression and messenger ribonucleic acid (mRNA) pro- membrane to become two (the latter is often considered to cessing. Connecting the two membranes are the nuclear be the reverse of the former). Membrane fission initially pores, large complexes of protein and nucleic acid that occurs when a vesicle forms from the endoplasmic reticu- form pores through which solutes and small proteins can lum in preparation for transport to the Golgi. One mem- pass between the nucleus and cytoplasm. For example, brane separates into two. When the vesicle arrives at the these pores actively transport subunits of deoxyribonucleic Golgi, membrane fusion occurs as the vesicle membrane acid (DNA) polymerase from the site of synthesis in the becomes one with the Golgi membrane. These dynamic cytoplasm to the nucleus, regulated by nuclear localization membrane processes preserve the integrity of the lumen signals in the amino acid sequence. Processed RNA is such that the lumen of the endoplasmic reticulum is in a actively transported from the nucleus to the cytoplasm sense common with the lumen of the Golgi and the sided- through the nuclear pores. See also: Nuclear Envelope and ness of the membranes is unchanged. See also: Endoplas- Lamins: Organization and Dynamics; Nuclear Pores: mic Reticulum to Golgi Transport: Methods; Protein Methods for Preparation; The Export from the Endoplasmic Reticulum to the Cytosol: Methods; Vesicle Transport Assay Mitochondrial membranes Golgi Mitochondria are constructed of a double membrane. Mitochondria are factories that make ATP, the common The Golgi is actually a series of stacked organelles that are energy currency of the cell. Oxidative phosphorylation in communication with each other through the vesicle takes place in mitochondria through complexes of proteins transport system described above. Extensive posttransla- in the inner mitochondrial membrane, very similar to oxi- tional modification of proteins occurs in the Golgi. Com- dative phosphorylation in bacteria. ATP synthesis is plex carbohydrate can be added to proteins here. Acylation achieved using the energy of the proton gradient across of some proteins (the addition of fatty acids or isoprenoids the inner mitochondrial membrane. This membrane has to membrane proteins) occurs in the Golgi. The Golgi is in a specialized lipid composition. In particular, dipho- turn in communication with the plasma membrane. Vesicle sphatidylglycerol, or cardiolipin, is exclusively found in the transport occurs between the Golgi and the plasma mem- mitochondria. The inner mitochondrial membrane is very brane, involving membrane fusion mediated by specialized low in sterol content and is very high in protein content. membrane proteins, as the vesicle membrane becomes one Accordingly, the mass ratio of lipid to protein is much with the plasma membrane. This transport process can lower in the inner mitochondrial membrane than in the deliver newly synthesized plasma membrane proteins to the plasma membrane. The outer membrane is relatively per- plasma membrane. It can also lead to secretion of soluble meable to small solutes. The mitochondria have a sophis- proteins synthesized originally in the endoplasmic reticu- ticated import system for proteins because some of the lum. See also: Golgi: Methods for Preparation; Membrane mitochondrial proteins are coded by nuclear DNA while

ENCYCLOPEDIA OF LIFE SCIENCES & 2009, John Wiley & Sons, Ltd. www.els.net 7 Cell Membrane Features others are coded by mitochondrial DNA. See also: wall outside the plasma membrane. The organelles within Mitochondria Protein Import: Methods; Mitochondria: plant cells are given their structure and function by mem- Structure and Role in Respiration; Oxidative Phosphoryl- branes, just as in the animal cells. The distribution, diver- ation; Plant Mitochondria sity and function of plant cell organelle membranes are different from those of animal cells in some cases. The most obvious example is the chloroplast. As in mitochondria, the Other Biological Membranes chloroplast is the site of ATP synthesis. The chloroplast is surrounded by a double membrane system. As in mito- In the following discussion of other biological membranes, chondria, the outer membrane is permeable to small sol- emphasis will be placed on distinctive features only, since utes. The inner membrane is not. Inside the chloroplast is a there are many features in common among all biological third membrane system, the thylakoid membranes, where membranes. conversion of light energy to chemical energy occurs. See also: Plant Chloroplasts and Other ; Plant Bacterial membranes Plasma Membrane Gram-positive bacteria, such as Streptococcus faecalis, have a plasma membrane surrounded by a cell wall. Virus membranes Membranes of Gram-negative bacteria, such as Escher- Some viruses are covered by a membrane. These are called ichia coli, have much in common with mitochondrial enveloped viruses. Examples include influenza and HIV membranes, including the ability to synthesize ATP using viruses. Viruses in some cases obtain their membranes by a proton gradient across the inner membrane of the bac- budding the nucleocapsid from the plasma membrane of terium. Two membranes surround the Gram-negative the host cell. In those cases, the viral membrane contains a bacteria separated by the periplasmic space. The outer subset of the lipid components of the host cell membrane, membrane is permeable to small solutes owing to the in the form of a lipid bilayer. However, host cell membrane presence of porins, large channel-forming proteins of the proteins are largely absent from the viral membranes. outer membrane. The inner membrane is capable of sup- Instead, the viral membrane proteins are usually coded for porting the required transmembrane proton gradient. An by the viral genome. These are transmembrane glyco- additional interesting feature of these bacterial membranes proteins that exhibit functions for binding to the target cell is the presence of a specialized active sugar transport sys- and for fusing with the target cell membrane. See also: Viral tem facilitated by a complex of proteins in the inner bac- Capsids and Envelopes: Structure and Function terial membrane. Intracellular membranes and organelles are absent in these prokaryotic organisms. See also: Bacterial Cells; Bacterial Cytoplasmic Membrane; Bac- terial Intracellular Membranes; Bacterial Membrane Further Reading Transport: Organization of Membrane Activities Alberts B, Johnson A, Lewis J et al. (2007) The Molecular Biology Plant cell membranes of the Cell, 5th edn. New York: Garland Press. Vance DE and Vance J (2008) Biochemistry of Lipids, Lipoproteins Plant cell membranes exhibit most of the characteristics of and Membranes, 5th edn. Amsterdam: Elsevier. eukaryotic animal cell membranes but plant cells are dis- Yeagle PL (2005) The Structure of Biological Membranes, 2nd edn. tinguished from most animal cells by the presence of a cell Boca Raton, FL: CRC Press.

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