Chapter 11 Cell Communication

Evolution of Cell Signaling A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response Each cell type secretes a mating factor that binds to receptors on the other cell type. Binding of the factors to receptors induces changes in the cell that lead to their fusion. © 2011 Pearson Education, Inc.

Yeast cell, mating type a Yeast cell, mating type  Figure 11.2  factor Receptor 1 Exchange of mating factors a  a factor Yeast cell, mating type a Yeast cell, mating type  2 Mating a  Figure 11.2 Communication between mating yeast cells. 3 New a/ cell a/

Gap junctions between animal cells Plasmodesmata between plant cells Figure 11.4 Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells (a) Cell junctions Figure 11.4 Communication by direct contact between cells. (b) Cell-cell recognition

3 Paracrine signaling- a secreting cell acts on nearby target cells by discharging molecules of local regulators -ex. Growth factor (stimulates cell growth and division) Synaptic signaling- nerve cell releases neurotransmitter molecules into a synapse stimulating target cell -ex. Nervous system

Neurotransmitter diffuses across synapse. Secreting cell Figure 11.5a Local signaling Target cell Electrical signal along nerve cell triggers release of neurotransmitter. Neurotransmitter diffuses across synapse. Secreting cell Secretory vesicle Figure 11.5 Local and long-distance cell signaling by secreted molecules in animals. Local regulator diffuses through extracellular fluid. Target cell is stimulated. (a) Paracrine signaling (b) Synaptic signaling

4 Specialized cells release hormone molecules into vessels of the circulatory system to travel to target cells in other parts of the body.

Long-distance signaling Figure 11.5b Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream. Target cell specifically binds hormone. Figure 11.5 Local and long-distance cell signaling by secreted molecules in animals. (c) Endocrine (hormonal) signaling

Target cell detects signaling molecule from outside of cell. Figure 11.6-1 EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 Reception Target cell detects signaling molecule from outside of cell. Signaling molecule binds to receptor protein on cell’s surface or inside. Receptor Figure 11.6 Overview of cell signaling. Signaling molecule

Relay molecules in a signal transduction pathway Figure 11.6-2 EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 Reception 2 Transduction Receptor Relay molecules in a signal transduction pathway Figure 11.6 Overview of cell signaling. Receptor protein changes in some way, initiating process of transduction. Converts a signal into a from that cause a response. Signaling molecule

Relay molecules in a signal transduction pathway Figure 11.6-3 EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Figure 11.6 Overview of cell signaling. Transduced molecules trigger a specific response. Ensures crucial activities occur in right cells at right time and proper conditions. Signaling molecule

Concept 11.2: Reception: A signaling molecule binds to a receptor protein, causing it to change shape A molecule that specifically binds to another molecule, often a larger one. Generally causes a receptor protein to undergo a shape change. © 2011 Pearson Education, Inc.

7 G protein functions as a switch inactive when GDP is attached

Signaling molecule binds to extracellular side of protein receptor activating it and causing a shape change. This allows G protein to bind and GDP is displaced by GTP.

Activated G protein dissociates from receptor, binds to enzyme, alters enzyme’s shape and activity. Triggers next step in pathway.

G protein also functions as GTPase enzyme, hydorlyzes bond GTP to GDP to leave enzyme and return to original state, available for reuse.

Binding to activated receptor and replacing GDP with GTP. to rapidly shut down pathway catalyzes the transfer of phosphate groups

14. Receptor tyrosine kinases (RTKs) are membrane receptors that attach phosphates to tyrosines 15. A receptor tyrosine kinase can trigger multiple signal transduction pathways at once © 2011 Pearson Education, Inc.

16 Receptors exist as individual polypeptides before signaling molecule binds.

17 Binding causes formation of dimer.

18 Dimerization activates tyrosine kinase region, each tyrosine kinase adds a phosphate group from an ATP to tyrosine.

19 Specific relay proteins recognize fully activated receptor. Each protein binds to a specific phosphorylated tyrosine resulting in structural change. 20. Each triggers a transduction pathway leading to a cellular response.

21 Gate remains closed until a ligand binds to the receptor.

22 Ligand binds, gate opens, specific ions flow in and rapidly change ion concentration inside cell.

Ligand dissociates from receptor, gate closes. nervous system

Intracellular Receptors 25. Intracellular receptor proteins are found in the cytosol or nucleus of target cells Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors Examples of hydrophobic messengers are the steroid and thyroid hormones of animals © 2011 Pearson Education, Inc.

Testosterone passes through plasma membrane. Binds to receptor Figure 11.9-2 Hormone (testosterone) EXTRACELLULAR FLUID Testosterone passes through plasma membrane. Plasma membrane Receptor protein Hormone- receptor complex Binds to receptor protein and activates it. DNA Figure 11.9 Steroid hormone interacting with an intracellular receptor. NUCLEUS CYTOPLASM

Enters nucleus and binds to specific genes. Hormone (testosterone) Figure 11.9-3 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex Enters nucleus and binds to specific genes. DNA Figure 11.9 Steroid hormone interacting with an intracellular receptor. NUCLEUS CYTOPLASM

Bound protein acts as transcription factor. Hormone (testosterone) Figure 11.9-4 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA Figure 11.9 Steroid hormone interacting with an intracellular receptor. mRNA Bound protein acts as transcription factor. NUCLEUS CYTOPLASM

mRNA is translated into a specific protein Hormone (testosterone) Figure 11.9-5 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA Figure 11.9 Steroid hormone interacting with an intracellular receptor. mRNA NUCLEUS mRNA is translated into a specific protein New protein CYTOPLASM

27. controls which genes are turned on or transcribed at a particular time in particular cells

Concept 11.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell 28. Multistep pathways can amplify a signal: A few molecules can produce a large cellular response Multistep pathways provide more opportunities for coordination and regulation of the cellular response © 2011 Pearson Education, Inc.

Protein Phosphorylation and Dephosphorylation 29. Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation © 2011 Pearson Education, Inc.

Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation © 2011 Pearson Education, Inc.

Relay molecule activated protein kinase 1. Figure 11.10 Signaling molecule Receptor Relay molecule activated protein kinase 1. Activated relay molecule Active pk1 transfers phosphate from ATP to pk 2, activating it Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP pk 2 phosphorylates pk 3 Phosphorylation cascade ADP Active protein kinase 2 P PP P i Figure 11.10 A phosphorylation cascade. Inactive protein kinase 3 ATP ADP pk 3 brings about cell’s response to signal P Protein phosphatases remove phosphates, making proteins inactive and available for reuse Active protein kinase 3 PP P i Inactive protein ATP ADP P Active protein Cellular response PP P i

Small Molecules and Ions as Second Messengers 31. The extracellular signal molecule (ligand) that binds to the receptor is a pathway’s “first messenger” Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion © 2011 Pearson Education, Inc.

32. Adenylyl cyclase catalyzes ATP to cAMP which activates Figure 11.12 First messenger (signaling molecule such as epinephrine) Adenylyl cyclase G protein G protein-coupled receptor GTP ATP 32. Adenylyl cyclase catalyzes ATP to cAMP which activates another protein leading to cellular responses Second messenger cAMP Figure 11.12 cAMP as a second messenger in a G protein signaling pathway. Protein kinase A Cellular responses

cAMP usually activates protein kinase A, which phosphorylates various other proteins A different signaling molecule activates a different receptor which activates an inhibitory G protein. © 2011 Pearson Education, Inc.

35 Bacteria colonizes the lining of small intestine and produces toxins. The toxin is an enzyme that modifies G protein involved in regulating salt and water secretion. Unable to hydrolyze GTP to GDP, it remains active continuously making cAMP. High concentrations of cAMP causes secretion of large amounts of salt and water. Leads to development of profuse diarrhea.

36. muscle contraction, secretion of certain substances, and cell division

Signaling molecule (first messenger) Figure 11.14-3 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein DAG GTP G protein-coupled receptor PIP2 Phospholipase C IP3 (second messenger) IP3-gated calcium channel Figure 11.14 Calcium and IP3 in signaling pathways. Various proteins activated Cellular responses Endoplasmic reticulum (ER) Ca2 Ca2 (second messenger) CYTOSOL

Nuclear and Cytoplasmic Responses 38. Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus The final activated molecule in the signaling pathway may function as a transcription factor © 2011 Pearson Education, Inc.

Inactive transcription factor Active transcription factor Figure 11.15 Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor Figure 11.15 Nuclear responses to a signal: the activation of a specific gene by a growth factor. Response P DNA Gene NUCLEUS mRNA

Other pathways regulate the activity of enzymes rather than their synthesis Signaling pathways can also affect the overall behavior of a cell, for example, changes in cell shape © 2011 Pearson Education, Inc.

Glucose 1-phosphate (108 molecules) Figure 11.16 Reception Binding of epinephrine to G protein-coupled receptor (1 molecule) Transduction Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104) Figure 11.16 Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine. Inactive phosphorylase kinase Active phosphorylase kinase (105) Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Response Glycogen Glucose 1-phosphate (108 molecules)

Cell A. Pathway leads to a single response. Figure 11.18a Signaling molecule Receptor Relay molecules Figure 11.18 The specificity of cell signaling. Response 1 Response 2 Response 3 Cell A. Pathway leads to a single response. Cell B. Pathway branches, leading to two responses.

Activation or inhibition Figure 11.18b Activation or inhibition Figure 11.18 The specificity of cell signaling. Response 4 Response 5 Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.

Signaling Efficiency: Scaffolding Proteins and Signaling Complexes 42. Scaffolding proteins are large relay proteins to which other relay proteins are attached Scaffolding proteins can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway © 2011 Pearson Education, Inc.

Three different protein kinases Figure 11.19 Signaling molecule Plasma membrane Receptor Three different protein kinases Figure 11.19 A scaffolding protein. Scaffolding protein

Concept 11.5: Apoptosis integrates multiple cell-signaling pathways 43. Components of the cell are chopped up and packaged into vesicles that are digested by scavenger cells Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells © 2011 Pearson Education, Inc.

Figure 11.20 Figure 11.20 Apoptosis of a human white blood cell. 2 m

Apoptotic Pathways and the Signals That Trigger Them 44. Caspases are the main proteases (enzymes that cut up proteins) that carry out apoptosis Apoptosis can be triggered by An extracellular death-signaling ligand DNA damage in the nucleus Protein misfolding in the endoplasmic reticulum © 2011 Pearson Education, Inc.

Cells undergoing apoptosis Figure 11.22 Cells undergoing apoptosis Space between digits 1 mm Interdigital tissue Figure 11.22 Effect of apoptosis during paw development in the mouse.