Plasma Membrane

1. Chemical composition of the plasmalemma 2. Models of cell membrane structure 3. Structure and functions of membrane proteins  carriers (transporters)  channels  receptors 4. Cell coat (glycocalyx) 5. Cell surface specializations 6. Intercellular junctions – types Plasma (cell) membrane

. Plasma membrane, synonym: plasmalemma (Gr. lemma = 'husk')  thickness – 8-10 nm (EM)  asymmetrical . Chemical composition:  lipids – 20-40%  phospholipids  steroids (cholesterol)  glycolipids – 2-10%  proteins – ~50%  hydrophobic – structural  hydrophilic – receptors and enzymes >30  carbohydrates – 10%  glycoproteins  glycolipids  glycocalyx 2 Prof. Dr. Nikolai Lazarov Functions of plasma membrane

. Plasma membrane, synonym: plasmalemma (Gr. lemma = 'husk')

3 Prof. Dr. Nikolai Lazarov Membrane models

. Overton’s concept (1880) – the first comprehensive theory of lipid membrane structure:  “lipid-impregnated barrier layer” . Gorter-Grendel model (1925)  phospholipids – lipid bilayer . Danielli-Davson ‘sandwich’ model Ernest Overton (1865-1933)  two protein layers peripherally  lipid bilayer centrally  hydrophilic (outside) pole  hydrophobic (inside) pole . Robertson model (1959) – EM studies  unit membrane . “Fluid mosaic model” – Singer & Nicolson (1972) . Atomic model (2001)  model of lipid bilayer  atomic structure of integral membrane proteins 4 Prof. Dr. Nikolai Lazarov Fluid mosaic model

. Lipid-protein mosaic model  structural skeleton – phospholipid double layer  globular proteins: Seymour  integral membrane proteins, Jonathan Singer (single-pass and multi-pass (1924-2017) transmembrane proteins)  peripheral proteins  freeze-fracture:  P-face (protoplasmic)  Е-face (extracellular)

Garth L. Nicolson (1943-)

5 Prof. Dr. Nikolai Lazarov Membrane proteins – structure and functions

. Membrane proteins:  ~50% w/w in the plasmalemma  synthesized in the rough endoplasmic reticulum  their molecules are completed in the Golgi apparatus  transported in vesicles to the cell surface . Functional categories:  transport proteins  structural proteins (membrane-anchored)  receptor proteins  enzymes

6 Prof. Dr. Nikolai Lazarov Transport proteins

. pumps:  transport ions – Na+-K+ ATPase  metabolic precursors of macromolecules – amino acids, sugar . carriers (transporters, permeases):  uniport (facilitated diffusion)  symport (cotransport) carriers  antiport (exchange diffusion) . channels – allow the passage of:  small ions and molecules  open and closed conformations  voltage-gated  ligand-gated  mechanically gated

7 Prof. Dr. Nikolai Lazarov Structural proteins

. Cell adhesion molecules:  typically transmembrane receptors

 homophilic and heterophilic binding . 5 protein families – 50 types:  Ca2+-dependent:  cadherins – E-, P- and N-  selectins – E-, L- and P-  integrins – 24 members  Ca2+-independent:  immunoglobulin superfamily • neural cell adhesion molecules • intercellular cell adhesion molecules • vascular cell adhesion molecules • platelet-endothelial cell adhesion molecule 8 Prof. Dr. Nikolai Lazarov Receptor proteins

. Membrane receptors:  neurotransmitter receptors  ionotropic channels  metabotropic receptors  hormone receptors  peptide hormone  steroid hormone  immune receptors  pattern recognition receptors  complement receptors  Fc receptors  B-cell receptors  T-cell receptors  endocytosis receptors – coated pits  clathrin-dependent endocytosis  internalization of iron  some growth factors 9  LDL receptors Prof. Dr. Nikolai Lazarov Scaffold proteins

. Scaffold proteins:  regulatory and morphogenetic  crucial regulators of many key signaling pathways  help localize pathway components to specific areas of the cell  maintain spatial relationships between enzymes and signaling proteins

10 Prof. Dr. Nikolai Lazarov Membrane-bound enzymes

. ~30 different enzymes:  Alkaline phosphatase  5I-Nucleotidase  АТPase  digestive enzymes  disaccharidases  dipeptidases

11 Prof. Dr. Nikolai Lazarov Cell coat (glycocalyx)

. First description – Yamada (1955) . Synonym = glycolemma  thickness – up to 100 nm  renewal – 6-8 h  PAS-positive . Chemical composition:  glycolipids – lipid rafts  cerebrosides  gangliosides  glycoproteins  proteoglycans  hyaluronic acid . Functions:  defense  absorption  immunologic role  cell recognition 12  cell adhesion Prof. Dr. Nikolai Lazarov Plasmalemmal-cytoskeletal organelles . Fractalosomes (Lat. fractus – broken) – 2 types: . Plasmalemmal-actin fractalosomes:  microvilli  stereovilli (stereocilia)  lamellipodia – cytoskeletal protein actin projections on the leading edge of the cell  filopodia (microspikes) – slender cytoplasmic projections that extend beyond the leading edge of lamellipodia in migrating cells  invadopodia (invasive feet) – protrusions in the cell membrane of some cells that are rich in actin and extend into the extracellular matrix  podosomes – cylindrical, actin-rich structures found on the outer surface of the plasma membrane of animal cells . Plasmalemmal-microtubule fractalosomes:  kinocilia – 9x2 + 2 microtubules

 sensocilia (single primary cilia) – 9x2 + 0 microtubules 13 Prof. Dr. Nikolai Lazarov Cell surface modifications

. 4 types structural specializations: (Gr. mikros, small + Lat. villus, tuft of hair) . Microvilli:  cytoplasmic processes, 1 µm high;0.08 µm wide  brush (striated) border  core of actin filaments  terminal web . Basal cell surface folds:  interdigitations . Stereocilia:  non-motile microvilli of unusual length  ductus epididymis  hair cells of the ear 14 . Cilia & Flagella Prof. Dr. Nikolai Lazarov Cilia

 motile cytoplasmic processes Gr. kinesis, movement + Lat. cilium, eyelash  in respiratory epithelia  capable of moving fluid and particles

 rapid back-and-forth movement  ATP is the source of energy for ciliary motion  movement rate 1/25 s 15 Prof. Dr. Nikolai Lazarov Kinocilia

length: 2-10 µm diameter: 0.3-0.5 µm

axoneme (central core): 9 doublets + 2 singlets 9 x 2 + 2

transitory part: microtubule organizing center

basal bodies (kinetosome): 9 triplets 9 x 3 + 0 16 Prof. Dr. Nikolai Lazarov Sensocilia

axoneme (central core):  Single primary cilia 9 doublets + 0 singlets 9 x 2 + 0

17 Prof. Dr. Nikolai Lazarov Flagellum

 much longer: 100-200 µm  limited to one flagellum per cell  in the human body only in spermatozoa

18 Prof. Dr. Nikolai Lazarov Kartagener’s syndrome

. immotile ciliary syndrome of Kartagener  a defect in the action of the cilia lining the respiratory tract and fallopian tube due Manes Kartagener (1897-1975) to the absense of dynein armes in them

. Chronic respiratory infections and male infertility:  chronic rhinitis  chronic sinusitis  chronic bronchitis  bronchiectasis  sterile males  females may be fertile

19 Prof. Dr. Nikolai Lazarov Intercellular junctions 3 types intercellular junctions (adhesiosomes): .

. Barrier (impermeable) junctions:  tight junction, zonula occludens  occluding strip, fascia occludens  occluding spot, macula occludens

. Adhering (anchoring) junctions:  punctum adhaerens

 belt desmosome, zonula adhaerens

 spot desmosome, macula adhaerens (Gr. desmos, band + soma, body) . Communicating junctions:  gap junction, nexus  synapse 2020 . Junctional complex Prof. Dr. Nikolai Lazarov Thank you…

21 Prof. Dr. Nikolai Lazarov