Chapter 11. Cell Communication

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1 Chapter 11 Cell Communication

2 Overview: The Cellular Internet Cell-to-cell communication Is absolutely essential for multicellular organisms

3 Concept 11.1: External signals are converted into responses within the cell

4 Evolution of Cell Signaling Yeast cells Identify their mates by cell signaling Figure Exchange of mating factors. Each cell type secretes a mating factor that binds to receptors on the other cell type. Mating. Binding of the factors to receptors induces changes in the cells that lead to their fusion. New a/α cell. The nucleus of the fused cell includes all the genes from the a and a cells. Receptor a Yeast cell, mating type a a α factor a/α α factor α Yeast cell, mating type α α

5 Signal transduction pathways Convert signals on a cell s surface into cellular responses Are similar in microbes and mammals, suggesting an early origin

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

7 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.

8 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.

9 In other cases, animal cells Communicate using local regulators (chemical signals (growth factors) secreted short distances) Local signaling Target cell Electrical signal along nerve cell triggers release of neurotransmitter Secretory vesicle Neurotransmitter diffuses across synapse Figure 11.4 A B Local regulator diffuses through extracellular fluid (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. Target cell is stimulated (b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell.

10 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 (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells.

11 Earl W. Sutherland Discovered how the hormone epinephrine acts on cells The Three Stages of Cell Signaling: A Preview

12 Sutherland suggested that cells receiving signals went through three processes Reception Transduction Response

13 Overview of cell signaling EXTRACELLULAR FLUID Plasma membrane CYTOPLASM 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signal molecule Figure 11.5

14 Concept 11.2: Reception: A signal molecule binds to a receptor protein, causing it to change shape

15 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

16 Intracellular receptors Are cytoplasmic or nuclear proteins Intracellular Receptors

17 Signal molecules that are small or hydrophobic And can readily cross the plasma membrane use these receptors In this way, information from outside the cell is transmitted into the cell

18 Steroid hormones Bind to intracellular receptors Hormone EXTRACELLULAR (testosterone) FLUID Receptor protein Plasma membrane Hormonereceptor complex 1 The steroid hormone testosterone passes through the plasma membrane. 2 Testosterone binds to a receptor protein in the cytoplasm, activating it. mrna NUCLEUS DNA New protein 3 The hormonereceptor complex enters the nucleus and binds to specific genes. 4 The bound protein stimulates the transcription of the gene into mrna. Figure 11.6 CYTOPLASM 5 The mrna is translated into a specific protein.

19 There are three main types of membrane receptors G-protein-linked osine kinases Ion channel Receptors in the Plasma Membrane

20 G-protein-linked receptors Signal-binding site Segment that interacts with G proteins G-protein-linked Receptor Plasma Membrane Activated Receptor Signal molecule Inctivate enzyme CYTOPLASM GDP G-protein (inactive) Enzyme GDP GTP Activated enzyme GTP GDP P i Figure 11.7 Cellular response

21 Receptor tyrosine kinases Signal molecule αhelix in the Membrane Signal-binding sitea Signal molecule osines CYTOPLASM Receptor tyrosine kinase proteins (inactive monomers) Dimer Activated relay proteins 6 ATP 6 ADP P P P P P P P P P P P P Cellular response 1 Cellular response 2 Figure 11.7 Activated tyrosinekinase regions (unphosphorylated dimer) Fully activated receptor tyrosine-kinase (phosphorylated dimer) Inactive relay proteins

22 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

23 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

24 At each step in a pathway The signal is transduced into a different form, commonly a conformational change in a protein Signal Transduction Pathways

25 Many signal pathways Include phosphorylation cascades Protein Phosphorylation and Dephosphorylation

26 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, deactivating it

27 A phosphorylation cascade Signal molecule Receptor Activated relay molecule 1 A relay molecule activates protein kinase 1. Figure 11.8 Inactive protein kinase 1 5 Inactive protein kinase 2 Enzymes called protein phosphatases (PP) catalyze the removal of the phosphate groups from the proteins, making them inactive and available for reuse. P i ATP Active protein kinase 1 PP ADP Inactive protein kinase 3 P i ATP Active protein kinase 2 PP ADP Inactive protein 2 Active protein kinase 1 transfers a phosphate from ATP to an inactive molecule of protein kinase 2, thus activating this second kinase. P i P ATP PP 3 Active protein kinase 3 Active protein kinase 2 then catalyzes the phosphorylation (and activation) of protein kinase 3. ADP P 4 Finally, active protein kinase 3 phosphorylates a protein (pink) that brings about the cell s response to the signal. Active protein P Cellular response

28 Second messengers Are small, nonprotein, water-soluble molecules or ions Small Molecules and Ions as Second Messengers

29 Cyclic AMP Cyclic AMP (camp) Is made from ATP NH 2 NH 2 NH 2 N N N N N N O O O N N N N O N N Adenylyl cyclase Phoshodiesterase O P O P O P O Ch 2 HO P O CH 2 CH 2 O O O O O O O O O Pyrophosphate P H 2 O P P O O i OH OH OH OH OH ATP Cyclic AMP AMP Figure 11.9

30 Many G-proteins Trigger the formation of camp, which then acts as a second messenger in cellular pathways First messenger (signal molecule such as epinephrine) G protein Adenylyl cyclase G-protein-linked receptor GTP ATP camp Protein kinase A Figure Cellular responses

31 Calcium, when released into the cytosol of a cell Acts as a second messenger in many different pathways (muscle contraction, secretion, cell division) Calcium ions and Inositol Triphosphate (IP 3 )

32 Calcium is an important second messenger Because cells are able to regulate its concentration in the cytosol EXTRACELLULAR FLUID Plasma membrane ATP Ca 2+ pump Mitochondrion Nucleus CYTOSOL ATP Ca 2+ pump Ca 2+ pump Endoplasmic reticulum (ER) Figure Key High [Ca 2+ ] Low [Ca 2+ ]

33 Other second messengers such as inositol triphosphate and diacylglycerol (IP3 and DAG) Can trigger an increase in calcium in the cytosol

34 1 A signal molecule binds to a receptor, leading to activation of phospholipase C. 2 Phospholipase C cleaves a plasma membrane phospholipid called PIP 2 into DAG and IP 3. 3 DAG functions as a second messenger in other pathways. EXTRA- CELLULAR FLUID Signal molecule (first messenger) G protein G-protein-linked receptor GTP Phospholipase C PIP 2 DAG IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) Ca 2+ Ca 2+ (second messenger) Various proteins activated Cellular response Figure IP 3 quickly diffuses through 5 Calcium ions flow out of 6 The calcium ions the cytosol and binds to an IP 3 gated calcium channel in the ER membrane, causing it to open. the ER (down their concentration gradient), raising the Ca 2+ level in the cytosol. activate the next protein in one or more signaling pathways.

35 Concept 11.4: Response: Cell signaling leads to regulation of cytoplasmic activities or transcription

36 In the cytoplasm Signaling pathways regulate a variety of cellular activities (especially with proteins) Cytoplasmic and Nuclear Responses

37 Cytoplasmic response to a signal Reception Binding of epinephrine to G-protein-linked receptor (1 molecule) Transduction Inactive G protein Active G protein (10 2 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (10 2 ) ATP Cyclic AMP (10 4 ) Inactive protein kinase A Active protein kinase A (10 4 ) Inactive phosphorylase kinase Active phosphorylase kinase (10 5 ) Inactive glycogen phosphorylase Active glycogen phosphorylase (10 6 ) Figure Response Glycogen Glucose-1-phosphate (10 8 molecules)

38 Other pathways Regulate genes by activating transcription factors that turn genes on or off Growth factor Receptor Reception Phosphorylation cascade Transduction CYTOPLASM Inactive transcription Active factor transcription factor P DNA Gene Response Figure NUCLEUS mrna

39 Signal pathways with multiple steps Can amplify the signal and contribute to the specificity of the response Fine-Tuning of the Response

40 Each protein in a signaling pathway Amplifies the signal by activating multiple copies of the next component in the pathway Signal Amplification

41 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 The Specificity of Cell Signaling

42 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 Response 2 3 Cell B. Pathway branches, leading to two responses Activation or inhibition Figure Cell C. Cross-talk occurs between two pathways Response 4 Response 5 Cell D. Different receptor leads to a different response

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

44 Signal response is terminated quickly By the reversal of ligand binding Termination of the Signal

45 Programmed cell death Caspases (enzymes are common for this) If death signaling ligand occupies cellsurface receptors then caspases are activated and apoptosis occurs Signals often come from mt, ER or nucleus Apoptosis

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