Chapter 11 Cell Communication PowerPoint Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 1
Overview: The Cellular Internet Cell-to-cell communication is essential for multicellular organisms Biologists have discovered some universal mechanisms of cellular regulation The combined effects of multiple signals determine cell response 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 2
Local and Long-Distance Signaling 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 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 3
Figure 11.4 Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells (a) Cell junctions Communication by direct connection and/or contact between cells (b) Cell-cell recognition 4
The Three Stages of Cell Signaling: A Preview Earl W. Sutherland discovered how the hormone epinephrine, which triggers the fight or flight response, acts on cells Sutherland suggested that cells receiving signals went through three processes: Reception Transduction Response Fight or flight response: Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Animation: Overview of Cell Signaling http://changingminds.org/explanations/brain/fight_flight.htm http://www.thebodysoulconnection.com/educationcenter/fight.html 5
Overview of cell signaling EXTRACELLULAR FLUID Plasma membrane CYTOPLASM 1 Reception 2 Transduction 3 Response Receptor Relay molecules in a signal transduction pathway Activation of cellular response Signaling molecule 6
1 Signaling molecule (ligand) Gate closed Ions Ligand-gated ion channel receptor Plasma membrane Membrane receptors ion channel receptors 2 Gate open Cellular response 3 Gate closed 7
Figure 11.2 Receptor factor 1 Exchange of mating factors a Communication between mating yeast cells Yeast cell, mating type a a factor Yeast cell, mating type 2 Mating a 3 New a/ cell a/ 8
Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell Signal transduction usually involves multiple steps 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 Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Signal Transduction Pathways The molecules that relay a signal from receptor to response are mostly proteins Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated At each step, the signal is transduced into a different form, usually a shape change in a protein Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 10
Protein Phosphorylation and Dephosphorylation In many pathways, the signal is transmitted by a cascade of protein phosphorylations Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 11
Signaling molecule A phosphorylation cascade Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 P i ATP PP ADP Active protein kinase 2 P Inactive protein kinase 3 P i ATP PP ADP Active protein kinase 3 P Inactive protein P i ATP PP ADP Active protein P Cellular response 12
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, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion Cyclic AMP (camp) and calcium ions are common second messengers Many signal molecules trigger formation of camp Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 13
First messenger G protein Adenylyl cyclase G protein-coupled receptor GTP ATP camp Second messenger camp as second messenger in a G-protein-signaling pathway Protein kinase A Cellular responses 14
EXTRACELLULAR FLUID CYTOSOL ATP ATP Mitochondrion Nucleus Ca 2+ pump Ca 2+ pump Plasma membrane Ca 2+ pump Endoplasmic reticulum (ER) Calcium ions (Ca 2+ ) act as a second messenger in many pathways Calcium is an important second messenger because cells can regulate its concentration Key High [Ca 2+ ] Low [Ca 2+ ] The maintenance of calcium ion concentrations in an animal cell 15
A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol Pathways leading to the release of calcium involve inositol triphosphate (IP 3 ) and diacylglycerol (DAG) as additional second messengers Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Animation: Signal Transduction Pathways 16
EXTRA- CELLULAR FLUID Signaling molecule (first messenger) Calcium and IP 3 in signaling pathways G protein DAG G protein-coupled receptor GTP Phospholipase C PIP 2 IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) Ca 2+ Various proteins activated Cellular responses CYTOSOL Ca 2+ (second messenger) 17
Response: Cell signaling leads to regulation of transcription or cytoplasmic activities The cell s response to an extracellular signal is sometimes called the output response Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities 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 may function as a transcription factor Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Growth factor Receptor Reception CYTOPLASM Inactive transcription factor Phosphorylatio n cascade Active transcription factor P Transduction Response Nuclear responses to a signal: the activation of a specific gene by a growth factor DNA Gene NUCLEUS mrna 19
Figure 11.9-5 Hormone (testosterone) EXTRACELLULAR FLUID Steroid hormone interacting with an intracellular receptor Receptor protein Plasma membrane Hormonereceptor complex mrna DNA NUCLEUS New protein CYTOPLASM 20
Reception Binding of epinephrine to G protein-coupled receptor (1 molecule) Transduction Inactive G protein Other pathways regulate the activity of enzymes Active G protein (10 2 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (10 2 ) Response 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 ) Glycogen Glucose-1-phosphate (10 8 molecules) Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine 21
RESULTS Wild-type (shmoos) Fus3 formin CONCLUSION 1 Mating factor G protein-coupled receptor Shmoo projection forming P Formin GDP Signaling pathways can also affect the physical characteristics of a cell, for example, cell shape 2 GTP Fus3 Phosphorylation cascade P Fus3 3 P Formin 4 Fus3 P Formin Actin subunit Microfilament 5 22
Fine-Tuning of the Response Multistep pathways have two important benefits: Amplifying the signal (and thus the response) Contributing to the specificity of the response Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 23
Signal Amplification Enzyme cascades amplify the cell s response At each step, the number of activated products is much greater than in the preceding step Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 24
The Specificity of Cell Signaling and Coordination of the Response Different kinds of cells have different collections of proteins These different proteins allow cells to detect and respond to different signals Even the same signal can have different effects in cells with different proteins and pathways Pathway branching and cross-talk further help the cell coordinate incoming signals Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 25
Signaling molecule Receptor Relay molecules The specificity of cell signaling Response 1 Cell A. Pathway leads to a single response. Response 2 Response 3 Cell B. Pathway branches, leading to two responses. Activation or inhibition Response 4 Response 5 Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response. 26
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 Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 27
A scaffolding protein Signaling molecule Plasma membrane Receptor Scaffolding protein Three different protein kinases 28
Termination of the Signal Inactivation mechanisms are an essential aspect of cell signaling When signal molecules leave the receptor, the receptor reverts to its inactive state Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 29
Concept 11.5: Apoptosis (programmed cell death) integrates multiple cell-signaling pathways Apoptosis is programmed or controlled cell suicide A cell is chopped and packaged into vesicles that are digested by scavenger cells Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 30
Apoptosis of human white blood cells 2 µm 31
Apoptosis in the Soil Worm Caenorhabditis elegans Apoptosis is important in shaping an organism during embryonic development The role of apoptosis in embryonic development was first studied in Caenorhabditis elegans In C. elegans, apoptosis results when specific proteins that accelerate apoptosis override those that put the brakes on apoptosis Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 32
Ced-9 protein (active) inhibits Ced-4 activity Mitochondrion Molecular basis of apoptosis in C. elegans Receptor for deathsignaling molecule Ced-4 Ced-3 Inactive proteins (a) No death signal Ced-9 (inactive) Cell forms blebs Deathsignaling molecule Active Ced-4 Active Ced-3 Other proteases Activation cascade Nucleases (b) Death signal 33
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 Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 34
Effect of apoptosis during paw development in the mouse Interdigital tissue 1 mm 35
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