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Cell Communication Chapter 11
Cell-to-cell communication is essential for multicellular organisms The combined effects of multiple signals determine cell response
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Evolution of Cell Signaling
Signal transduction pathway – how a signal on a cell’s surface is converted into a specific cellular response Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes The concentration of signaling molecules allows bacteria to detect population density Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Yeast cell, mating type a Yeast cell, mating type
Fig. 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 New a/ cell a/ 3
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Communication among bacteria
Fig. 11-3 Communication among bacteria 1 Individual rod- shaped cells 2 Aggregation in process 0.5 mm 3 Spore-forming structure (fruiting body) Figure 11.3 Communication among bacteria Fruiting bodies
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Cells in a multicellular organism communicate by chemical messengers
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
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Local signaling Local regulator Target cell Neurotransmitter
Fig. 11-5ab Local signaling Target cell Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Secreting cell Secretory vesicle Figure 11.5 Local and long-distance cell communication in animals Local regulator diffuses through extracellular fluid Target cell is stimulated (a) Paracrine signaling (b) Synaptic signaling
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Long-distance signaling
Fig. 11-5c Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Figure 11.5 Local and long-distance cell communication in animals Target cell (c) Hormonal signaling
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The Three Stages of Cell Signaling: A Preview
Fig The Three Stages of Cell Signaling: A Preview EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Figure 11.6 Overview of cell signaling Signaling molecule
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Concept 11.2: Reception: A signal molecule binds to a receptor protein, causing it to change shape
The binding between a signal molecule (ligand) and receptor is highly specific A shape change in a receptor is often the initial transduction of the signal Most signal receptors are plasma membrane proteins Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane There are three main types of membrane receptors: G protein-coupled receptors Receptor tyrosine kinases Ion channel receptors Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Segment that interacts with G proteins Signaling-molecule binding site
G protein-coupled receptor - plasma membrane receptor that works with the help of a G protein G protein acts as an on/off switch If GDP is bound to the G protein, the G protein is inactive Figure 11.7 Membrane receptors—G protein-coupled receptors, part 1 Segment that interacts with G proteins G protein-coupled receptor
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Fig. 11-7b Plasma membrane G protein-coupled receptor Inactive enzyme
Activated receptor Signaling molecule GDP G protein (inactive) Enzyme GDP GTP CYTOPLASM 1 2 Activated enzyme Figure 11.7 Membrane receptors—G protein-coupled receptors, part 2 GTP GDP P i Cellular response 3 4
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Receptor tyrosine kinases - membrane receptors that attach phosphates to tyrosines
can trigger multiple signal transduction pathways at once Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Fully activated receptor tyrosine kinase
Fig. 11-7c Signaling molecule (ligand) Ligand-binding site Signaling molecule Helix Tyr Tyr Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins Dimer CYTOPLASM 1 2 Activated relay proteins Figure 11.7 Membrane receptors—receptor tyrosine kinases 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 P Tyr P 6 ATP 6 ADP Activated tyrosine kinase regions Fully activated receptor tyrosine kinase Inactive relay proteins 3 4
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Allows ions, such as Na+ or Ca2+ through a channel in the receptor
Fig. 11-7d 1 Signaling molecule (ligand) Gate closed Ions Ligand-gated ion channel - receptor acts as a gate when the receptor changes shape Allows ions, such as Na+ or Ca2+ through a channel in the receptor Plasma membrane Ligand-gated ion channel receptor 2 Gate open Cellular response Figure 11.7 Membrane receptors—ion channel receptors 3 Gate closed
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Small or hydrophobic chemical messengers
Intracellular Receptors - found in the cytosol or nucleus of target cells Small or hydrophobic chemical messengers Ex. hormone-receptor complex can act as a transcription factor, turning on specific genes Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA Figure 11.8 Steroid hormone interacting with an intracellular receptor mRNA NUCLEUS New protein CYTOPLASM
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Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell Signal transduction usually involves multiple steps and can amplify a signal and/or provide opportunities for coordination and regulation of the response 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
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Phosphorylation cascade
Fig. 11-9 Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP Phosphorylation cascade ADP Active protein kinase 2 P PP P i Figure 11.9 A phosphorylation cascade Inactive protein kinase 3 ATP ADP Active protein kinase 3 P PP P i Inactive protein ATP ADP P Active protein Cellular response PP P i
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Small Molecules and Ions as Second Messengers
The extracellular signal molecule that binds to the receptor is a pathway’s “first messenger” Second messengers - small, nonprotein, water-soluble molecules or ions that spread throughout participate in pathways initiated by G protein-coupled receptors and receptor tyrosine kinases Ex. Cyclic AMP and calcium ions Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Cyclic AMP (cAMP) - one of the most widely used second messengers
Fig Cyclic AMP (cAMP) - one of the most widely used second messengers Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal Adenylyl cyclase Phosphodiesterase Pyrophosphate P P i ATP cAMP AMP Figure Cyclic AMP
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Fig First messenger Adenylyl cyclase G protein G protein-coupled receptor GTP ATP Second messenger cAMP usually activates protein kinase A, which phosphorylates various other proteins Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase cAMP Figure cAMP as second messenger in a G-protein-signaling pathway Protein kinase A Cellular responses
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Calcium ions (Ca2+) act as a second messenger in many pathways
Fig EXTRACELLULAR FLUID Calcium ions (Ca2+) act as a second messenger in many pathways important because cells can regulate its concentration Plasma membrane Ca2+ pump ATP Mitochondrion Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers Nucleus CYTOSOL Ca2+ pump Endoplasmic reticulum (ER) Figure The maintenance of calcium ion concentrations in an animal cell Ca2+ pump ATP Key High [Ca2+] Low [Ca2+]
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EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein
Fig 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 Calcium and IP3 in signaling pathways Endoplasmic reticulum (ER) Various proteins activated Cellular responses Ca2+ Ca2+ (second messenger) CYTOSOL
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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 transcription factor regulate the activity of enzymes affect the physical characteristics of a cell, for example, cell shape Figure Nuclear responses to a signal: the activation of a specific gene by a growth factor Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Growth factor Reception Receptor Nuclear responses to a signal: the activation of a specific gene by a growth factor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor Figure Nuclear responses to a signal: the activation of a specific gene by a growth factor Response P DNA Gene NUCLEUS mRNA
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Glucose-1-phosphate (108 molecules)
Fig Reception Binding of epinephrine to G protein-coupled 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) Figure Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine Inactive phosphorylase kinase Active phosphorylase kinase (105) Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Response Glycogen Glucose-1-phosphate (108 molecules)
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Fine-Tuning of the Response
Multistep pathways have two important benefits: Amplifying the signal (and thus the response) Contributies to the specificity of the response 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
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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
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Cell B. Pathway branches, leading to two responses.
Fig a Signaling molecule Receptor Relay molecules Figure The specificity of cell signaling Response 1 Response 2 Response 3 Cell A. Pathway leads to a single response. Cell B. Pathway branches, leading to two responses.
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Cell C. Cross-talk occurs between two pathways.
Fig b Activation or inhibition Figure The specificity of cell signaling Response 4 Response 5 Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.
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Signaling Efficiency: Scaffolding Proteins and Signaling Complexes
Scaffolding proteins - large relay proteins to which other relay proteins are attached increase the signal transduction efficiency by grouping together different proteins involved in the same pathway 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
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Signaling Plasma molecule membrane Receptor Three different protein
Fig Signaling molecule Plasma membrane Receptor Three different protein kinases Figure A scaffolding protein Scaffolding protein
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Apoptosis - programmed or controlled cell suicide
Concept 11.5: Apoptosis (programmed cell death) integrates multiple cell-signaling pathways Apoptosis - programmed or controlled cell suicide chopped and packaged into vesicles that are digested by scavenger cells prevents enzymes from leaking out of a dying cell and damaging neighboring cells important in shaping an organism during embryonic development Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Apoptosis of human white blood cells
Fig Apoptosis of human white blood cells Figure Apoptosis of human white blood cells 2 µm
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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 Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Fig Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals Interdigital tissue 1 mm Figure Effect of apoptosis during paw development in the mouse
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