Chapter 11 Cell Communication Power Point Lectures for

Chapter 11 Cell Communication Power. Point Lectures for Biology, Seventh Edition Neil Campbell and Jane Reece Lectures by Chris Romero Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• Concept 11. 1: External signals are converted into responses within the cell Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Evolution of Cell Signaling • Yeast cells – Identify their mates by cell signaling 1 Exchange of mating factors. Each cell type secretes a mating factor that binds to receptors on the other cell type. 2 Mating. Binding factor Receptor a Yeast cell, factor Yeast cell, mating type a of the factors to receptors induces changes in the cells that lead to their fusion. a 3 New a/ cell. Figure 11. 2 The nucleus of the fused cell includes all the genes from the a and a cells. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings a/

• Signal transduction pathways – Convert signals on a cell’s surface into cellular responses – Are similar in microbes and mammals, suggesting an early origin Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Local and Long-Distance Signaling • Cells in a multicellular organism – Communicate via chemical messengers 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

• In other cases, animal cells – Communicate using local regulators 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) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell.

• In long-distance signaling – Both plants and animals use hormones 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

The Three Stages of Cell Signaling: A Preview • Earl W. Sutherland – Discovered how the hormone epinephrine acts on cells At the time, the big unanswered question was how a molecule could effect a change inside a cell without actually crossing the cell membrane Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• Sutherland suggested that cells receiving signals went through three processes – Reception – Transduction – Response Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• Overview of cell signaling EXTRACELLULAR FLUID 1 Reception CYTOPLASM Plasma membrane 2 Transduction 3 Response 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• The binding between signal molecule (ligand) – And receptor is highly specific • 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 • Intracellular receptors – Are cytoplasmic or nuclear proteins Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• 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 G-protein-linked Receptor Plasma Membrane Activated Receptor Signal molecule GDP CYTOPLASM G-protein (inactive) Enzyme GDP GTP Activated enzyme GTP GDP P i Figure 11. 7 Cellular response Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Inctivate enzyme

• Receptor tyrosine kinases Signal-binding sitea Signal molecule Helix in the Membrane Tyrosines Tyr CYTOPLASM Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins (inactive monomers) Tyr Dimer Activated relay proteins Figure 11. 7 Tyr P Tyr Tyr P Tyr Tyr 6 ATP 6 ADP Activated tyrosinekinase regions (unphosphorylated dimer) Fully activated receptor tyrosine-kinase (phosphorylated dimer) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 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: Transduction: 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 protein kinases add a phosphate to the next one in line, activating it – Phosphatase 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 Figure 11. 8 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 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 de Enzymes called protein 5 phosphatases (PP) catalyze the removal of the phosphate groups from the proteins, making them inactive and available for reuse. ATP a sc Inactive protein kinase 3 ca PP 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

Cyclic AMP • Cyclic AMP (c. AMP) – 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 c. AMP, 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, when released into the cytosol of a cell – Acts as a second messenger in many different pathways Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• 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+]

• Other second messengers such as inositol triphosphate and diacylglycerol – Can trigger an increase in calcium in the cytosol Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

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 cytoplasmic activities or transcription Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Cytoplasmic and Nuclear Responses • In the cytoplasm – Signaling pathways regulate a variety of cellular activities 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 Figure 11. 13 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Glycogen Glucose-1 -phosphate (108 molecules)

• 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings m. RNA

Fine-Tuning of the Response • Signal pathways with multiple steps – Can amplify the signal and contribute to the specificity of the response Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Signal Amplification • Each protein in a signaling pathway – Amplifies the signal by activating multiple copies of the next component in the pathway Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

The Specificity of Cell Signaling • The different combinations of proteins in a cell – Give the cell great specificity in both the signals it detects and the responses it carries out Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• Pathway branching and “cross-talk” – Further help the cell coordinate incoming signals Signal molecule Receptor Relay molecules Cell A. Pathway leads to a single response Response 1 Response 2 3 Cell B. Pathway branches, leading to two responses Activation or inhibition Figure 11. 15 Cell C. Cross-talk occurs between two pathways Response 4 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Response 5 Cell D. Different receptor leads to a different response

Signaling Efficiency: Scaffolding Proteins and Signaling Complexes • Scaffolding proteins – Can increase the signal transduction efficiency Signal molecule Plasma membrane Receptor Scaffolding protein Figure 11. 16 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Three different protein kinases

Termination of the Signal • Signal response is terminated quickly – By the reversal of ligand binding Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings