Chapter 11 Cell Communication

Overview: Cellular Messaging Cell-to-cell communication is essential for both multicellular and unicellular organisms Biologists have discovered some universal mechanisms of cellular regulation Cells most often communicate with each other via chemical signals For example, the fight-or-flight response is triggered by a signaling molecule called epinephrine © 2011 Pearson Education, Inc.

Figure 11.1 Figure 11.1 How does cell signaling trigger the desperate flight of this gazelle?

Evolution of Cell Signaling The yeast, Saccharomyces cerevisiae, has two mating types, a and  Cells of different mating types locate each other via secreted factors specific to each type 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 Signal transduction pathways convert signals on a cell’s surface into cellular responses © 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/

Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes The concentration of signaling molecules allows bacteria to sense local population density © 2011 Pearson Education, Inc.

Individual rod-shaped cells Figure 11.3 1 Individual rod-shaped cells 2 Aggregation in progress 0.5 mm 3 Spore-forming structure (fruiting body) 2.5 mm Figure 11.3 Communication among bacteria. Fruiting bodies

Cell communication: Direct Contact Cells in a multicellular organism communicate by chemical messengers Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells In local signaling, animal cells may communicate by direct contact, or cell-cell recognition © 2011 Pearson Education, Inc.

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

In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances In long-distance signaling, plants and animals use chemicals called hormones The ability of a cell to respond to a signal depends on whether or not it has a receptor specific to that signal © 2011 Pearson Education, Inc.

Figure 11.5 Local signaling Long-distance signaling Target cell Electrical signal along nerve cell triggers release of neurotransmitter. Endocrine cell Blood vessel Neurotransmitter diffuses across synapse. Secreting cell Secretory vesicle Hormone travels in bloodstream. Target cell specifically binds hormone. Local regulator diffuses through extracellular fluid. Target cell is stimulated. Figure 11.5 Local and long-distance cell signaling by secreted molecules in animals. (a) Paracrine signaling (b) Synaptic signaling (c) Endocrine (hormonal) signaling

The Three Stages of Cell Signaling: A Preview Earl W. Sutherland discovered how the hormone epinephrine acts on cells Sutherland suggested that cells receiving signals went through three processes Reception Transduction Response © 2011 Pearson Education, Inc.

Animation: Overview of Cell Signaling Right-click slide / select “Play” © 2011 Pearson Education, Inc. 13

A signaling molecule binds to a receptor protein, causing it to change shape The binding between a signal molecule (ligand) and receptor is highly specific; hydrophilic ligands & membrane receptors, hydrophobic ligands & intracellular receptors. A shape change in a receptor is often the initial transduction of the signal Most receptors are plasma membrane proteins © 2011 Pearson Education, Inc.

Receptors in the Plasma Membrane Most water-soluble signal molecules bind to specific sites on receptor proteins that span the plasma membrane There are three main types of membrane receptors: G protein-coupled receptors Receptor tyrosine kinases Ion channel receptors © 2011 Pearson Education, Inc.

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

Calcium Ions and Inositol Triphosphate (IP3) Calcium ions (Ca2+) act as a second messenger in many pathways A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol Pathways causing the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers © 2011 Pearson Education, Inc.

Animation: Signal Transduction Pathways Right-click slide / select “Play” © 2011 Pearson Education, Inc. 18

Signaling molecule (first messenger) Figure 11.14-1 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. Endoplasmic reticulum (ER) Ca2 CYTOSOL

Signaling molecule (first messenger) Figure 11.14-2 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. Endoplasmic reticulum (ER) Ca2 Ca2 (second messenger) CYTOSOL

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

Signaling Efficiency: Scaffolding Proteins and Signaling Complexes 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 In some cases, scaffolding proteins may also help activate some of the relay proteins © 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

Nuclear and Cytoplasmic Responses Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities The response may occur in the cytoplasm or in the nucleus 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.

G Protein-Coupled Receptors G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors (receptors for vision, taste, hormones, etc.) Many opiates and pharmaceuticals are GPCR ligands A GPCR is a plasma membrane receptor that works with the help of a G protein The G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive GDP & GTP are structurally the same as ATP except with a guanine instead of an adenine. © 2011 Pearson Education, Inc.

G Protein-Coupled Receptors GPCR receives signal GPCR activates a G protein by exchanging a GTP for a GDP G protein binds to effector protein to activate it Effector protein initiates a response

G protein-coupled receptor Plasma membrane Activated receptor Figure 11.7b G protein-coupled receptor Plasma membrane Activated receptor Signaling molecule Inactive enzyme GTP GDP GDP CYTOPLASM G protein (inactive) Enzyme GTP 1 2 GDP Activated enzyme Figure 11.7 Exploring: Cell-Surface Transmembrane Receptors GTP GDP P i 3 Cellular response 4

G Protein-Coupled Receptors Once an effector protein has been activated it elicits some sort of cellular response Enzymatic activity (catalyzes a specific substrate or initiates an kinase cascade) Produce a second messenger; cAMP, IP and DAG, Ca2+ CPCR’s are deactivated when GTP that is attached to the effector is hydrolyzed

G protein-coupled receptor Plasma membrane Activated receptor Figure 11.7b G protein-coupled receptor Plasma membrane Activated receptor Signaling molecule Inactive enzyme GTP GDP GDP CYTOPLASM G protein (inactive) Enzyme GTP 1 2 GDP Activated enzyme Figure 11.7 Exploring: Cell-Surface Transmembrane Receptors GTP GDP P i 3 Cellular response 4

G Protein-Coupled Receptors Glycogen breakdown occurs when a ligand (epinephrine) binds to a receptor activates a G protein activates an effector  activates a second messenger (cAMP) activates a protein kinase  activates an enzyme to remove glucose from glycogen to increase blood sugar levels.

Abnormal functioning of RTKs is associated with many types of cancers Receptor tyrosine kinases (RTKs) are membrane receptors that attach phosphates to tyrosines A receptor tyrosine kinase can trigger multiple signal transduction pathways at once Abnormal functioning of RTKs is associated with many types of cancers © 2011 Pearson Education, Inc.

Signaling molecule (ligand) Ligand-binding site Figure 11.7c Signaling molecule (ligand) Ligand-binding site  helix in the membrane Signaling molecule Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr CYTOPLASM Receptor tyrosine kinase proteins (inactive monomers) Dimer 1 2 Activated relay proteins Figure 11.7 Exploring: Cell-Surface Transmembrane Receptors Cellular response 1 Tyr Tyr P Tyr Tyr P Tyr Tyr P P Tyr Tyr P Tyr Tyr P Tyr Tyr P P Cellular response 2 Tyr Tyr P Tyr Tyr P Tyr Tyr P 6 ATP 6 ADP P Activated tyrosine kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine kinase (phosphorylated dimer) Inactive relay proteins 3 4

Receptor Tyrosine Kinase (RTK) Deactivation of RTK’s occurs when enzymes remove phosphate groups from the kinases or when endocytosis occurs.

The Role of RTK Insulin is the ligand binds to RTK (receptor) RTK forms dimer & phosphorylation occurs  insulin response protein  signal cascade muscles store glucose as glycogen, other cells bring glucose into cells, liver cell store glucose as glycogen, fat cells convert glucose into fat.

Comparing RTK & GPCR RTK GPCR Directly responsible for signal transduction pathway Indirectly responsible for signal transduction pathway Multiple pathways are possible Single pathway

Gated Ion Receptors A ligand-gated ion channel receptor acts as a gate when the receptor changes shape When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor © 2011 Pearson Education, Inc.

Signaling molecule (ligand) Figure 11.7d 1 2 3 Gate closed Ions Gate open Gate closed Signaling molecule (ligand) Plasma membrane Ligand-gated ion channel receptor Cellular response Figure 11.7 Exploring: Cell-Surface Transmembrane Receptors

Gated Ion Receptors Acetylcholine (ligand)  binds to ligand-gated receptor  gates open allowing Na+ to enter the cell  initiates a nerve impulse.

Intracellular Receptors Intracellular receptor proteins are found in the cytosol or nucleus of target cells Small or hydrophobic/lipid soluble chemical messengers can readily cross the membrane and activate receptors Examples of hydrophobic/lipid soluble messengers are the steroid and thyroid hormones of animals An activated hormone-receptor complex can act as a transcription factor, turning on/off specific genes © 2011 Pearson Education, Inc.

Hormone (testosterone) EXTRACELLULAR FLUID Figure 11.9-1 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein DNA Figure 11.9 Steroid hormone interacting with an intracellular receptor. NUCLEUS CYTOPLASM

Hormone (testosterone) EXTRACELLULAR FLUID Figure 11.9-2 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA Figure 11.9 Steroid hormone interacting with an intracellular receptor. NUCLEUS CYTOPLASM

Hormone (testosterone) EXTRACELLULAR FLUID Figure 11.9-3 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA Figure 11.9 Steroid hormone interacting with an intracellular receptor. NUCLEUS CYTOPLASM

Hormone (testosterone) EXTRACELLULAR FLUID 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 NUCLEUS CYTOPLASM

Hormone (testosterone) EXTRACELLULAR FLUID 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 New protein CYTOPLASM

Intracellular Receptors Testosterone/estrogen (ligand) diffuse across cell membrane  bind to receptor protein in cytoplasm  the complex will move to nucleus  causes transcription of genes  testosterone causes sperm production and production of muscle fibers ; estrogen causes cells of the uterus to prepare for pregnancy and mammary cells genes are deactivated.

Concept 11.5: Apoptosis integrates multiple cell-signaling pathways Apoptosis is programmed or controlled cell suicide 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

Ced-9 protein (active) inhibits Ced-4 activity Figure 11.21 Ced-9 protein (active) inhibits Ced-4 activity Ced-9 (inactive) Cell forms blebs Death- signaling molecule Mitochondrion Active Ced-4 Active Ced-3 Other proteases Ced-4 Ced-3 Nucleases Receptor for death- signaling molecule Activation cascade Figure 11.21 Molecular basis of apoptosis in C. elegans. Inactive proteins (a) No death signal (b) Death signal

Apoptotic Pathways and the Signals That Trigger Them 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.

Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers © 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.

Cancer Growth factor(ligand) activates protein kinase receptor activates RAS protein (relay protein)  initiates a cascade  activates a transcription factor  attaches to a gene  gene produces p53  protein 53 checks DNA for damage If the DNA is repaired the cell can continue with cell division, if not the cell is directed to die (apoptosis) If p53 is faulty then the cell will go through cell division even if the DNA is damaged which leads to cancer. © 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