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contents Principles of Biology 20 Cells use signaling and receptors to communicate.

An channel viewed from above. Ion channels permit of information across the . They are special pore­like structures that only allow certain to pass through them. Shown is a view down the center of an , a short tunnel that an ion must flow through to pass across a cell membrane. © 2009 Nature Publishing Group Hilf, R.J.C. & Dutzler, R. Structure of a potentially open state of a proton­activated pentameric ­gated ion channel. Nature 457, 115–118 (2009) doi: 10.1038/nature07461. Used with permission.

Topics Covered in this Module

Cell­Cell Communication Receptors

Major Objectives of this Module

Describe different ways cells can communicate with each other. Outline the steps of transduction. Compare and contrast types found in cells. Explain how ­linked receptors lead to . Explain how activation of a G ­coupled receptor leads to signal transduction.

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contents Principles of Biology

20 Cell Signaling

Cell­Cell Communication Trillions of cells in the body, with hundreds of different cell types, must recognize each other, coordinate activity and respond to stimuli. The consequences can be dire if there is a mistake in this intricate system. For example, cancerous tumors grow when fail to recognize cells as "non­self." So how do cells communicate and respond to each other? Can cells in an also interact with cells from other ? Does cellular structure influence communication? Using environmental cues, or "," and signal receptors, cells interact with each other. These interactions occur primarily between molecules.

How do cells communicate with each other? A dolphin whistles to identify itself to a group. Birds convey alarm with calls to the flock when danger is near. Cells likewise communicate with each other in response to environmental cues. For example, single­celled organisms such as may coordinate a group response using or aggregation. Many single­celled , such as , are surprisingly social organisms that interact with each other to find mating partners. Cues that stimulate responses and communication include light or heat, touch or , and — most frequently — chemicals. The mechanisms that cells use to share information are common to many diverse species and underscore the interconnectedness among all .

The underlying mechanism used by cells to share information is signal transduction, which produces cellular responses to extracellular signals. Chemical cell signaling in multicellular eukaryotes involves information exchange between neighboring cells as well as with those farther afield. Together, the various signaling mechanisms allow the cells of a to coordinate activities that maintain the organism's overall functioning.

Numerous chemicals are involved in the language of cells. Cells that respond to a are called sensory cells. These cells secrete , signaling molecules that bind directly to receptors on target cells to produce biological responses. The assortment of signaling molecules includes , chemical messengers secreted by , and , chemicals produced by the . These chemicals, among others, serve as signals that cue target cells to respond in a particular way to alter the of an organism. These signals are received by receptors on the target cell that act as signal detectors.

Different types of signals are grouped according to the distance they travel to reach their targets. targets receptors in the same cell that originated the signal. targets cells near the signaling cell. Paracrine signals diffuse through extracellular fluid to reach their destination. Endocrine signaling involves hormones that target distant cells. The ferries hormones to facilitate long­distance communication.

Adjacent cells can use direct contact to communicate locally. In , gap junctions provide transmission channels between adjacent cells. Gap junctions are pores in the cell membrane that allow cells to share molecules and ions. A protein called aggregates in groups of six in the plasma membrane. The resulting structure, called a , pairs with a connexon from the adjoining cell. The paired create a pore through which small molecules and ions can travel. Plasmodesmata are the plant counterpart to gap junctions. A third mechanism by which direct contact can be used to transmit information is through cell­cell recognition. For example, in human embryogenesis, large cell surface called allow similar cells to recognize each other and aggregate to form specialized tissues.

The nervous system plays a key role in multicellular animals. Communication between the of is accomplished with the release of neurotransmitters, which diffuse across the synaptic cleft. Although this synaptic contact does not involve a physical connection between two neurons, it provides the functional connection between the neurons. For example, an can transmit a signal along a presynaptic axon. At the between neurons, the information is transmitted from the presynaptic site to the postsynaptic site using neurotransmitters. Such long­distance signals, originating in the brain and extending to an animal's farthest extremities, allow for centralized communication in the nervous system.

Do cells transmit signals internally? Downstream activation is a cascading sequence in which an initial signaling event triggers further events that transmit the signal to other proteins in the cell. Ligands initiate intracellular messaging, and other chemicals called relay molecules pass around information within the cell. Test Yourself

Explain three ways by which cells communicate with each other.

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Like pieces of a puzzle, signaling ligands must be specific to their receptors (Figure 1). Once the receptor receives its specific chemical signal, it changes its three­dimensional shape, which in turn alters its activity. Receptor­ligand binding is reversible, which is essential because it allows the biological activity of the receptor to be switched off (or on) after the ligand is released. A ligand that activates the biological activity of a receptor is known as an . In some cases, agonist binding can also be prevented by binding of an inhibitory , called an antagonist, to the receptor. In this situation, the antagonist blocks binding of the agonist to the receptor, blocking the normal of the receptor.

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Figure 1: Receptor structure enables binding of appropriate ligand. The chemical structure of a receptor matches a specific ligand. When the ligand binds to the correct receptor, subsequent molecular reactions inside the cell can occur. Ligands that activate and deactivate a receptor's biological function are known as and antagonists, respectively. © 2011 Nature Education All rights reserved.

How is a cell able to respond to the signals it receives? Internal and external cellular structures determine how a cell responds to environmental signals. Receptors are located on the cell surface as well as within the cell, in the or the nucleus. Transmembrane receptors bind to large, hydrophilic molecules that cannot enter the cell by crossing through the bilayer of the plasma membrane. There are three major types of transmembrane receptors: ion channel­linked receptors, enzyme­linked receptors and ­ coupled receptors. The binding sites of transmembrane receptors are typically oriented toward the exterior of the cell, although the receptor directs the signal inward.

Intracellular nuclear and cytoplasmic receptors directly bind smaller, hydrophobic molecules that readily diffuse through the cell membrane. Such molecules include the hormones and testosterone, which are derivatives of , a lipid­soluble molecule. Steroid hormones bind to intracellular receptors, causing those receptors to change shape. The ­receptor complex then moves into the nucleus, where it binds to a specific DNA region called the hormone response element (HRE). By binding to the HRE, the hormone­receptor complex induces or represses the expression of specific (Figure 2). Those genes then either begin or cease the synthesis of their corresponding proteins, resulting in a metabolic response that ultimately alters the physiology of the body.

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Figure 2: signaling pathway. The chemical structure of a receptor matches a specific ligand. When the ligand binds to the correct receptor, subsequent molecular reactions inside the cell can occur. © 2014 Nature Education All rights reserved.

Test Yourself

What are the differences between transmembrane and cytoplasmic receptors? How do these differences influence function?

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Signal transduction occurs in three major stages (Figure 3). Similar to how a key fits into a lock, signal reception occurs when a signaling molecule binds to its receptor. This action initiates the signal transduction pathway, usually by inducing a in the receptor. Transduction occurs when the receptor is activated as a result of its conformational change and transmits, or transduces, the signal to other molecules within the cell. Transduction often involves , , or another form of chemical transformation. Phosphorylated and dephosphorylated molecules can become relay molecules, inducing subsequent cell reactions. The final phase in the pathway is the response, when the transduced signal initiates a reaction from the cell, such as a change in expression or metabolic activity.

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Figure 3: Signal transduction occurs in three steps. Reception, transduction and response are the three steps common to all signal transduction pathways. The cellular responses vary depending on the particular pathway but usually result in changes in gene expression. © 2014 Nature Education All rights reserved. Figure Detail

Test Yourself

What three steps make up signal transduction?

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Various receptors bind signaling molecules with different degrees of affinity. Affinity refers to the strength with which a ligand binds to an enzyme, receptor, or . Most and receptors have specific conformations that confer high affinity. For example, most enzymes have high affinity for their substrates, so that the substrate remains in the active site long enough for the enzyme to catalyze a reaction. In contrast, many of the common transport proteins have low affinity, which allows the release of the transported molecule from the protein to proceed relatively easily. The concentrations of ligands also influence their binding to the receptors on target cells. As the ligand concentration decreases, the likelihood of ligands binding to the receptors on target cells and thus triggering a response also decreases.

What kinds of responses can result? Most cellular responses to extracellular stimulation require signal transduction. Such responses include short­term effects such as enzyme activation and cell movement. Long­term responses include gene activation and gene expression. Cell survival, and death are also mediated by signal transduction. Stimuli from the environment, such as the volatile chemicals in perfume, can initiate signal transduction and prompt a response. When receptors on olfactory sensory neurons bind these chemicals and send that information to the brain, the event is perceived by the brain as a fragrance.

The sophistication of an organism's signal transduction pathways generally corresponds to the organism's structural complexity. In single­celled organisms, such as bacteria, signal transduction allows for an effective mode of communication. For example, the bacterium Salmonella enteritidis uses the chemical acyl homoserine lactone to signal growth and increase (Figure 4). Individual bacteria secrete acyl homoserine lactone to communicate their presence to other bacteria and induce them to form aggregates with one another. When a critical density, or quorum, of bacteria is reached, acyl homoserine lactone concentration reaches a threshold, changing its function. At this higher concentration, acyl homoserine lactone instead signals the aggregated bacteria to begin invading their host organism, causing disease. Yeasts, such as Candida albicans, use a similar mechanism of . When nutrient­deprived, , brewer's , transmits mating factors to initiate reproduction. http://www.nature.com/principles/ebooks/principles­of­biology­104015/29144952/1 4/6 2015/3/8 Cell Signaling | Principles of Biology from Nature Education

Figure 4: Salmonella enteritidis. This bacteria's ability to communicate to other individuals via signal transduction has led to increased incidence of food poisoning in the developed world. Scimat/Science Source.

Basic research: Sensory transduction. Sensory biologists study the molecular processes that drive sensory transduction, focusing on the role of those processes in cellular architecture. One example is the transient receptor potential (TRP) ion channel family in the fruit fly Drosophila melanogaster. In photoreceptor cells, TRP channels transduce light stimuli into electric signals. TRP channels are widely expressed in the sensory systems of , including humans. They function in both auditory transduction and olfaction as well as touch and detection. As progress continues toward understanding the mechanisms underlying TRP channel function, disorders such as Usher syndrome, which can cause deafness and blindness, might be targeted for therapy. Many more TRP channel mechanisms await discovery.

Controversy. With so much still unknown about sensory transduction, uncertainty surrounds proposed TRP channel function theories. In particular, scientists dispute mechanisms underlying cold temperature perception. A Spanish team of sensory biologists published a paper in 2008 arguing that temperature signal transduction differs between visceral sensory neurons, found in many internal organs, and somatic sensory neurons found elsewhere. These neurons use subsets of the TRP channel family — TRPA1 and TRPM8, respectively — and scientists hypothesize that those channels play a key role in the perception of pain caused by cold . More recently, in 2010, members of the team suggested that TRPM8 also plays a role in generating tears in the cold to keep the eyes moist. Although other researchers dispute the theories, scientists believe research on TRPM8 and TRPA1 could help develop that target abdominal pain receptors.

IN THIS MODULE

Cell­Cell Communication Receptors Summary Test Your Knowledge

WHY DOES THIS TOPIC MATTER?

Synthetic Biology: Making Life from Bits and Pieces Scientists are combining biology and engineering to change the world.

Stem Cells Stem cells are powerful tools in biology and medicine. What can scientists do with these cells and their incredible potential?

Cancer: What's Old Is New Again Is cancer ancient, or is it largely a product of modern times? Can cutting­edge research lead to prevention and treatment strategies that could make cancer obsolete?

PRIMARY LITERATURE http://www.nature.com/principles/ebooks/principles­of­biology­104015/29144952/1 5/6 2015/3/8 Cell Signaling | Principles of Biology from Nature Education

Innovation in Cannabis medicine potentiation of glycine receptors contributes to cannabis­induced analgesia. View | Download

Inhibitors may block entry of hepatitis C into cells EGFR and EphA2 are host factors for entry and possible targets for antiviral therapy. View | Download

How can nematodes help reduce obesity in humans? A whole­organism screen identifies new regulators of fat storage. View | Download

Classic paper: Breakthrough enables tiny measurements of ion channel activity (1976) Single­channel currents recorded from membrane of denervated frog muscle fibers. View | Download

Adaptor proteins regulate cell signaling Structural basis for regulation of the Crk signaling protein by a switch. View | Download

Mitochondria change shape to help the cell survive During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. View | Download

SCIENCE ON THE WEB

What Do Your Teeth Have to Do with Bacterial Communication? Scientist Bonnie Bassler explains quorum sensing, a bacterial communication phenomenon

An Interactive on Cell Responses. Send a signal to a plant of animal cells.

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contents Principles of Biology

20 Cell Signaling

Receptors Three major types of transmembrane receptors — the ion channel­linked receptors, enzyme­linked receptors and G protein­coupled receptors — play a role in signal transduction. Why does the cell need three kinds of receptors, and what specific role does each play in facilitating cell signaling?

What are ion channel­linked receptors? Ubiquitous among cells, ion channels are transmembrane proteins that act as pores, allowing passage of ions such as sodium, and potassium into and out of cells. However, not all ion channels are open at all times. Many are gated — they are initially closed and require an external stimulus before they open and permit ions to pass through. An important class of ion channel is the ion channel­linked receptors (Figure 5). These ion channels, initially closed, contain a receptor site that accepts a specific ligand. Upon binding of the ligand, the ion channel undergoes a conformational change that results in the opening of the channel. The ligands that activate ion channel­linked receptors are frequently neurotransmitters, and ion channel­linked receptors are often associated with the nervous system. Research suggests that ion channel­linked receptors mediate the effects of alcohol and anesthesia, among other functions.

Figure 5: Ion channel­linked receptors permit ion flow depending on the presence of specific ligands. Before an ion channel­linked receptor binds with its specific ligand, the channel is closed, preventing ion flow (1). When the ligand binds to receptors in the channel protein, a conformational change causes the channel to open (2), and ions begin flowing through the channel protein (3). When the ligand is no longer present, the conformational change reverses, and the channel closes, ending ion flow (4). © 2014 Nature Education All rights reserved.

What do enzyme­linked receptors do? Like all transmembrane receptors, enzyme­linked receptors contain two domains. The extracellular domain contains a receptor for a signaling ligand, such as a hormone or a . Upon binding, the ligand induces enzymatic activity in the intracellular domain. Most frequently, these receptors are linked to , which are enzymes that phosphorylate other molecules by transferring a group from another molecule, usually triphosphate (ATP), to them. Receptor kinases (Figure 6) are an important class of enzyme­linked receptors. When two receptor tyrosine proteins are activated by ligand binding, they dimerize, forming a complex and activating their kinase domains. The close proximity of the two receptor tyrosine kinases allows them to phosphorylate each other at specific tyrosine residues. Inactive relay or adapter proteins then bind the phosphorylated tyrosine residues and become activated, relaying the signal to other parts of the cell and initiating cellular responses.

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Figure 6: Receptor tyrosine kinases. Receptor tyrosine kinases are transmembrane receptors. When they bind to their ligands, they phosphorylate each other, triggering cellular events. © 2014 Nature Education All rights reserved.

Test Yourself

How does a receptor initiate signal transduction?

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What is the purpose of G protein­coupled receptors? G protein­coupled receptors (GPCRs) perform a wide variety of functions, but their structures always feature a receptor containing seven membrane­spanning domains. Inactive G proteins are bound to (GDP), a closely related to ATP. An example of a GPCR in action is the binding of epinephrine to its receptor to increase the availability of blood glucose during times of stress (Figure 7). When epinephrine binds to the GPCR, the GPCR undergoes a conformational change that allows it to bind to the inactive G protein. The G protein is induced to exchange its GDP with (GTP) from the cytoplasm, which results in activation of the G protein. The activated G protein then diffuses along the membrane to activate an enzyme, which in turn initiates the next steps in the signaling cascade. At the end of the process, the G protein hydrolyzes its GTP into GDP, thereby returning the G protein to the inactive state.

Figure 7: The epinephrine signal transduction pathway in liver cells. http://www.nature.com/principles/ebooks/principles­of­biology­104015/29144952/2 2/4 2015/3/8 Cell Signaling | Principles of Biology from Nature Education

The epinephrine receptor is a membrane­spanning G protein­coupled receptor. Binding of epinephrine to the receptor triggers the activation of a G protein. The activated G protein activates the enzyme , which catalyzes the formation of the second messenger cyclic AMP (cAMP) from ATP. cAMP activates other enzymes including A, which phosphorylates and activates other signal transduction molecules. The signaling cascade initiated by epinephrine binding induces many physiological and gene expression changes that result in increased availability of glucose in the blood, including breakdown of glycogen and inhibition of glycogen synthesis. © 2014 Nature Education All rights reserved.

Sometimes the cell must deactivate a signal receptor through any one of a variety of mechanisms. Deactivation can serve to control a signal. Through such control, the cell can coordinate multiple signals and pathways. Test Yourself

How does activation of a G protein­coupled receptor initiate signal transduction?

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Cell signaling also exhibits two other hallmarks. The initial signaling event triggered by ligand­receptor binding is frequently amplified during subsequent transduction steps. For example, the binding of one hormone molecule to a may result in the phosphorylation of 10 proteins, and each of the 10 proteins may activate another 10 proteins, so that one hormone molecule indirectly triggers the activation of 100 proteins. This amplification enables a small signal to elicit a large cellular response and is an important mechanism in positive responses. In addition, it is critical that cells be able to easily deactivate cell signaling, and they are able to do so through a variety of mechanisms, such as the degradation of a ligand or the dephosphorylation of a receptor. Deactivation prevents a cellular response from inappropriately persisting after the signaling event has ended. For example, if a cell could not inactivate a growth factor signal directing it to divide, the cell would divide uncontrollably, resulting in tumor formation and cancer. Through amplification and deactivation of cell signaling events, a cell can coordinate multiple signals and pathways and formulate an appropriate physiological response.

Future perspectives. Discoveries in genomics often lead to novel therapies. A particularly promising area of research is G protein­ coupled receptors. Nearly half of all drugs currently in use target this receptor superfamily, and the biological importance of GPCRs is highlighted by the 2012 Nobel Prize in Chemistry, awarded to Brian Kobilka and Robert Lefkowitz for their work on GPCRs. Thousands of GPCRs are encoded by the human genome, many of which are "orphan" receptors that lack any known ligand. The functions of these receptors are not clearly understood. Scientists are trying to assess the potential functions the receptors perform. Without detailed genetic information, however, researchers must use a reverse approach to determine which orphan receptors may be effective drug targets. By developing chemicals that serve as agonists and/or antagonists to a receptor, scientists can identify the receptor's active ligands, leading them to better understand the receptor's function and its implications in health and disease.

IN THIS MODULE

Cell­Cell Communication Receptors Summary Test Your Knowledge

WHY DOES THIS TOPIC MATTER?

Synthetic Biology: Making Life from Bits and Pieces Scientists are combining biology and engineering to change the world.

Stem Cells Stem cells are powerful tools in biology and medicine. What can scientists do with these cells and their incredible potential?

Cancer: What's Old Is New Again Is cancer ancient, or is it largely a product of modern times? Can cutting­edge research lead to prevention and treatment strategies that could make cancer obsolete?

PRIMARY LITERATURE

Innovation in Cannabis medicine Cannabinoid potentiation of glycine receptors contributes to cannabis­induced analgesia. View | Download

Inhibitors may block entry of hepatitis C into cells EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets http://www.nature.com/principles/ebooks/principles­of­biology­104015/29144952/2 3/4 2015/3/8 Cell Signaling | Principles of Biology from Nature Education for antiviral therapy. View | Download

How can nematodes help reduce obesity in humans? A whole­organism screen identifies new regulators of fat storage. View | Download

Classic paper: Breakthrough enables tiny measurements of ion channel activity (1976) Single­channel currents recorded from membrane of denervated frog muscle fibers. View | Download

Adaptor proteins regulate cell signaling Structural basis for regulation of the Crk signaling protein by a proline switch. View | Download

Mitochondria change shape to help the cell survive During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. View | Download

SCIENCE ON THE WEB

What Do Your Teeth Have to Do with Bacterial Communication? Scientist Bonnie Bassler explains quorum sensing, a bacterial communication phenomenon

An Interactive on Cell Responses. Send a signal to a plant of animal cells.

page 104 of 989 2 pages left in this module

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contents Principles of Biology

20 Cell Signaling Summary

OBJECTIVE Describe different ways cells can communicate with each other. Autocrine and paracrine signals are forms of local cell communication. Autocrine signaling targets receptors within the same cell that originated the signal. Paracrine signaling targets receptors near the cell that originated the signal. Endocrine signals are a form of long­distance cell communication.

OBJECTIVE Outline the steps of signal transduction. Signal transduction takes place in three basic steps. Reception occurs when a signaling molecule binds to a receptor. Transduction occurs when the receptor is activated as a result of its conformational change and transmits the signal to another molecule. The response is the final phase in the pathway, occurring when the transduced signal initiates a physiological reaction from the cell.

OBJECTIVE Compare and contrast receptor types found in cells. Transmembrane receptors, including ion channel­linked receptors, enzyme­linked receptors and G protein­coupled receptors, bind to large, hydrophilic molecules that cannot enter the cell by crossing through the of the plasma membrane. The binding sites of transmembrane receptors are usually situated on the cell surface, although the receptor directs the signal inward. Intracellular nuclear and cytoplasmic receptors directly bind smaller, lipid­soluble molecules, such as steroid hormones, that readily diffuse through the cell membrane.

OBJECTIVE Explain how enzyme­linked receptors lead to signal transduction. Receptor tyrosine kinases are examples of enzyme­linked receptors that must dimerize to transmit a signal. This receptor contains an extracellular domain that binds ligands and an intracellular domain that acts as the kinase. When ligands bind to two receptor tyrosine kinase molecules, the receptors dimerize and form a complex, activating the kinase domain of the receptors and allowing the receptors to phosphorylate each other. The resulting phosphorylation of the complex leads to signal transduction and subsequent cellular responses.

OBJECTIVE Explain how activation of a G protein­coupled receptor leads to signal transduction. G protein­coupled receptors feature seven membrane­spanning domains. Upon binding signaling molecules, the receptor facilitates an inactive G protein's exchange of GDP for GTP. The G protein, now activated, diffuses along the membrane and binds to and activates enzymes to trigger the next signal transduction event.

Key Terms

affinity The strength with which a ligand binds to its receptor, enzyme, transport protein or other binding partner.

autocrine signaling A form of cell signaling in which the target cell is the same cell that originated the signal.

cytoplasmic receptor An that binds directly to smaller hydrophobic ligands, such as steroid hormones, that can diffuse through the lipid bilayer of the membrane.

direct contact A form of cell signaling in which adjacent cells communicate with each other via cell surface proteins that bind each other.

downstream activation Cascading sequence of intracellular signaling events triggered after the initial binding of a signaling molecule to its receptor.

endocrine signaling A form of cell signaling that involves long­range signals (hormones) that are transmitted to distant cells through the circulatory system.

enzyme­linked receptor One of three major types of transmembrane receptors; ligand­receptor binding activates an enzymatic activity in the receptor that results in further signal transduction events.

G protein­coupled receptor (GPCR) One of three major types of transmembrane receptors; uses G proteins as an intracellular signaling molecule.

hormone Substance produced in a small amount in one site and transported via the circulatory system to a target at another site in the organism.

ion channel­linked receptor that opens and closes in response to the binding of specific ligands; allows passage of specific ion types across a cell membrane. http://www.nature.com/principles/ebooks/principles­of­biology­104015/29144952/3 1/3 2015/3/8 Summary of Cell Signaling | Principles of Biology from Nature Education

kinase A type of enzyme that catalyzes the phosphorylation of proteins and other molecules.

ligand A molecule that binds directly to a receptor or other binding partner.

paracrine signaling A form of cell signaling in which a cell signals to other cells in its immediate vicinity via diffusible signaling molecules.

reception The first phase of signal transduction in which a signaling molecule binds to a receptor.

response The third and final phase of signal transduction in which a cell experiences a physiological change, such as changes in or gene expression, as a result of an extracellular signal.

signal transduction The overall process by which cells respond to extracellular signaling molecules or other stimuli by executing a physiological response.

synaptic contact A form of cell signaling in which two adjacent cells are not physically linked but separated by a small gap; diffusible molecules such as neurotransmitters are used to communicate between the two cells.

transmembrane receptor A receptor that spans the plasma membrane of a cell; binds to hydrophilic molecules that cannot pass through the lipid bilayer of the membrane; triggers intracellular responses.

IN THIS MODULE

Cell­Cell Communication Receptors Summary Test Your Knowledge

WHY DOES THIS TOPIC MATTER?

Synthetic Biology: Making Life from Bits and Pieces Scientists are combining biology and engineering to change the world.

Stem Cells Stem cells are powerful tools in biology and medicine. What can scientists do with these cells and their incredible potential?

Cancer: What's Old Is New Again Is cancer ancient, or is it largely a product of modern times? Can cutting­edge research lead to prevention and treatment strategies that could make cancer obsolete?

PRIMARY LITERATURE

Innovation in Cannabis medicine Cannabinoid potentiation of glycine receptors contributes to cannabis­induced analgesia. View | Download

Inhibitors may block entry of hepatitis C into cells EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy. View | Download

How can nematodes help reduce obesity in humans? A whole­organism screen identifies new regulators of fat storage. View | Download

Classic paper: Breakthrough enables tiny measurements of ion channel activity (1976) Single­channel currents recorded from membrane of denervated frog muscle fibers. View | Download

Adaptor proteins regulate cell signaling Structural basis for regulation of the Crk signaling protein by a proline switch. http://www.nature.com/principles/ebooks/principles­of­biology­104015/29144952/3 2/3 2015/3/8 Summary of Cell Signaling | Principles of Biology from Nature Education View | Download

Mitochondria change shape to help the cell survive During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. View | Download

SCIENCE ON THE WEB

What Do Your Teeth Have to Do with Bacterial Communication? Scientist Bonnie Bassler explains quorum sensing, a bacterial communication phenomenon

An Interactive on Cell Responses. Send a signal to a plant of animal cells.

page 105 of 989 1 pages left in this module

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contents Principles of Biology

20 Cell Signaling

Test Your Knowledge

1. What is the significance of distance in cell­to­cell communication?

Types of signals can be defined according to the distance they travel to reach their targets. Neighboring cells can communicate with each other, while distant cells are unable to communicate with each other. Gap junctions allow transduction of the most distant signal. Synaptic transmission is only effective as a mechanism for distant communication. None of the answers are correct.

2. Which of the following is true of a receptor tyrosine kinase?

Part of it is exposed to the , and part of it is located on the inside of the cell. It is a cytoplasmic receptor. It has seven transmembrane­spanning domains. Dimerization is an optional step in receptor tyrosine kinase activation. None of the answers are correct.

3. How are G protein­coupled receptors continually made available for reuse?

The G protein­mediated activation of the enzyme is only temporary. The G protein opens multiple binding sites simultaneously. When a G protein activates, it diffuses away from the receptor, leaving it available for reuse. Any signal can bind a G protein­coupled receptor. None of the answers are correct.

4. Why is the kinase so important in a receptor tyrosine kinase?

Tyrosine kinases activate synapses, triggering cellular responses. Tyrosine kinase is the signal that the receptor binds. Kinases transfer , phosphorylating the receptor. The tyrosine kinase domains are active in their monomeric states. The tyrosine kinase uses guanosine triphosphate to become activated.

Submit

IN THIS MODULE

Cell­Cell Communication Receptors Summary Test Your Knowledge

WHY DOES THIS TOPIC MATTER?

Synthetic Biology: Making Life from Bits and Pieces Scientists are combining biology and engineering to change the world.

Stem Cells Stem cells are powerful tools in biology and medicine. What can scientists do with these cells and their incredible potential? http://www.nature.com/principles/ebooks/principles­of­biology­104015/29144952/4 1/2 2015/3/8 Cell Signaling | Principles of Biology from Nature Education

Cancer: What's Old Is New Again Is cancer ancient, or is it largely a product of modern times? Can cutting­edge research lead to prevention and treatment strategies that could make cancer obsolete?

PRIMARY LITERATURE

Innovation in Cannabis medicine Cannabinoid potentiation of glycine receptors contributes to cannabis­induced analgesia. View | Download

Inhibitors may block entry of hepatitis C into cells EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy. View | Download

How can nematodes help reduce obesity in humans? A whole­organism screen identifies new regulators of fat storage. View | Download

Classic paper: Breakthrough enables tiny measurements of ion channel activity (1976) Single­channel currents recorded from membrane of denervated frog muscle fibers. View | Download

Adaptor proteins regulate cell signaling Structural basis for regulation of the Crk signaling protein by a proline switch. View | Download

Mitochondria change shape to help the cell survive During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. View | Download

SCIENCE ON THE WEB

What Do Your Teeth Have to Do with Bacterial Communication? Scientist Bonnie Bassler explains quorum sensing, a bacterial communication phenomenon

An Interactive on Cell Responses. Send a signal to a plant of animal cells.

page 106 of 989

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