Chapter 11 Cell Communication Copyright 2005 Pearson Education

Chapter 11 Cell Communication Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Concept 11. 1: • Cells in a multicellular organism – Communicate via chemical messengers • pathways – Convert signals on a cell’s surface into cellular responses Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Animal and plant cells • Have cell junctions that directly connect the cytoplasm of adjacent cells Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells Figure 11. 3 (a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

In local signaling, animal cells • May communicate via direct contact Figure 11. 3 (b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Other animal cells may • Communicate using signal molecules over short distances Local signaling Target cell Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Secretory vesicle Local regulator diffuses through extracellular fluid Figure 11. 4 A B (a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Target cell is stimulated (b) A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell.

In long-distance signaling • Both plants and animals use Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell Figure 11. 4 (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all C body cells. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Overview of cell signaling EXTRACELLULAR FLUID 1 CYTOPLASM Plasma membrane 2 3 Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signal molecule Figure 11. 5 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Concept 11. 2: • Reception: A signal molecule binds to a receptor protein, causing it to change shape • The binding between signal molecule receptor is highly specific and • A conformational change in a receptor is often the initial transduction of the signal Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Intracellular Receptors • Are cytoplasmic or nuclear proteins • Signal molecules that are small or hydrophobic and can readily cross the plasma membrane use these receptors Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Steroid hormones – Bind to intracellular receptors Hormone EXTRACELLULAR (testosterone) FLUID 1 The steroid hormone testosterone passes through the plasma membrane. Plasma membrane Receptor protein Hormonereceptor complex 2 Testosterone binds to a receptor protein in the cytoplasm, activating it. The hormone 3 DNA Figure 11. 6 receptor complex enters the nucleus and binds to specific genes. m. RNA The bound protein 4 NUCLEUS stimulates the transcription of the gene into m. RNA. CYTOPLASM Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings New protein The m. RNA is 5 translated into a specific protein.

Receptors in the Plasma Membrane • There are three main types of membrane receptors – G-protein-linked – Tyrosine kinases – Ion channel Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

G-protein-linked receptors Signal-binding site Segment that interacts with G proteins 1. G-protein-linked Receptor Plasma Membrane 2. Activated Receptor Signal molecule GDP CYTOPLASM G-protein (inactive) GDP Enzyme Activated enzyme 3. GTP 4. GDP P i Figure 11. 7 Cellular response Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Inctivate enzyme

Receptor tyrosine kinases 1. Signal-binding sitea Signal molecule 2. Signal molecule Helix in the Membrane Tyrosines Tyr CYTOPLASM Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins (inactive monomers) 4. Tyr P Tyr Tyr P Tyr Tyr 6 ATP 6 ADP Activated tyrosinekinase regions (unphosphorylated dimer) Tyr Dimer 3. Figure 11. 7 Tyr Fully activated receptor tyrosine-kinase (phosphorylated dimer) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Activated relay proteins P Tyr P Tyr P Inactive relay proteins Cellular response 1 Cellular response 2

Ion channel receptors Signal molecule (ligand) Gate closed Ions Ligand-gated ion channel receptor Plasma Membrane Gate open Cellular response Gate close Figure 11. 7 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Concept 11. 3: • Cascades of molecular interactions relay signals from receptors to target molecules in the cell • Multistep pathways – Can amplify a signal – Provide more opportunities for coordination and regulation Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Signal Transduction Pathways • At each step in a pathway – The signal is transduced into a different form, commonly a conformational change in a protein Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Protein Phosphorylation and Dephosphorylation • Many signal pathways – Include phosphorylation cascades Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• In this process – A series of add a phosphate to the next one in line, activating it – enzymes then remove the phosphates Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• A phosphorylation cascade Signal molecule Receptor Activated relay molecule Inactive protein kinase 1 1 A relay molecule activates protein kinase 1. ory ph ATP Inactive protein kinase 3 Enzymes called protein 5 phosphatases (PP) catalyze the removal of the phosphate groups from the proteins, making them inactive and available for reuse. Figure 11. 8 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings ATP Pi ADP Active protein kinase 3 PP Inactive protein P Finally, active protein 4 kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the signal. ATP ADP P i PP e ad sc PP ca on Pi Active protein kinase 2 3 then catalyzes the phosphorylation (and activation) of protein kinase 3. P Active protein kinase 2 ADP i lat Inactive protein kinase 2 os Ph Active protein kinase 1 2 transfers a phosphate from ATP to an inactive molecule of protein kinase 2, thus activating this second kinase. Active protein kinase 1 P Active protein Cellular response

Small Molecules and Ions as Second Messengers • Second messengers – Are small, nonprotein, water-soluble molecules or ions Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Second messengers • – Is made from ATP NH 2 N N O O O N N – O P O P O Ch 2 O O O NH 2 O Pyrophosphate P Pi N N Adenylyl cyclase O OH OH N N O CH 2 ATP Figure 11. 9 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Phoshodiesterase O P O O OH Cyclic AMP N N O HO P O CH 2 O O H 2 O OH OH AMP

• Many G-proteins – Trigger the formation of which then acts as a second messenger in cellular pathways First messenger (signal molecule such as epinephrine) G protein G-protein-linked receptor Adenylyl cyclase GTP ATP c. AMP Protein kinase A Figure 11. 10 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cellular responses

Calcium ions and Inositol Triphosphate (IP 3) • Calcium is an important second messenger – Because cells are able to regulate its concentration in the cytosol EXTRACELLULAR FLUID Plasma membrane Ca 2+ pump Mitochondrion ATP Nucleus CYTOSOL Ca 2+ pump ATP Figure 11. 11 Key Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ca 2+ pump Endoplasmic reticulum (ER) High [Ca 2+] Low [Ca 2+]

Calcium ions and Inositol Triphosphate (IP 3) • Inositol triphosphate is a second messenger that – Can trigger an increase in the cytosol Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings in

Calcium ions and Inositol Triphosphate (IP 3) 1 2 A signal molecule binds Phospholipase C cleaves a to a receptor, leading to plasma membrane phospholipid activation of phospholipase C. called PIP 2 into DAG and IP 3. EXTRACELLULAR FLUID 3 DAG functions as a second messenger in other pathways. Signal molecule (first messenger) G protein DAG GTP G-protein-linked receptor Phospholipase C PIP 2 IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) Ca 2+ (second messenger) Figure 11. 12 4 IP 3 quickly diffuses through the cytosol and binds to an IP 3– gated calcium channel in the ER membrane, causing it to open. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Various proteins activated 5 Calcium ions flow out of the ER (down their concentration gradient), raising the Ca 2+ level in the cytosol. Cellular response 6 The calcium ions activate the next protein in one or more signaling pathways.

Concept 11. 4: • Response: Cell signaling leads to regulation of or Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Cytoplasmic response to a signal Reception Binding of epinephrine to G-protein-linked 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) Inactive phosphorylase kinase Active phosphorylase kinase (105) Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Response Glycogen Glucose-1 -phosphate (108 molecules) Figure 11. 13 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Other pathways • Regulate genes by activating transcription factors that turn genes on or off Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription Active transcription factor P Response DNA Gene Figure 11. 14 NUCLEUS m. RNA Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Termination of the Signal • Signal response is terminated quickly – By the removal of bound ligand from its receptor Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings