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Cell Communication Chapter 11 Cell Communication.

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Presentation on theme: "Cell Communication Chapter 11 Cell Communication."— Presentation transcript:

1 Cell Communication Chapter 11 Cell Communication

2 Overview: Cellular Messaging  Cell-to-cell communication is essential for both multicellular and unicellular organisms  Biologists have discovered some universal mechanisms of cellular regulation  Cells most often communicate with each other via chemical signals  For example, the fight-or-flight response is triggered by a signaling molecule called epinephrine

3 Cells Recognize and Respond to External Signals Microbes provide a glimpse of the role of cell signaling in the evolution of life

4 Evolution of Cell Signaling  The yeast, Saccharomyces cerevisiae, has two mating types, a and   different mating types locate each other via secreted factors  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 Exchange of mating factors Receptor  factor a factor Yeast cell, mating type a Yeast cell, mating type  Mating New a/  cell a a a/   

5 Individual rod-shaped cells Spore-forming structure (fruiting body) Aggregation in progress Fruiting bodies mm 2.5 mm Communication in Bacteria: Cell Signaling Quorum sensing to signal other cells to gather!

6 Signaling in Multiceullar Organisms: “Local Signaling”  Multicellular organism’s cells 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

7 Figure 11.4 Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells (a) Cell junctions (b) Cell-cell recognition

8  In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances  The ability of a cell to respond to a signal depends on whether or not it has a receptor specific to that signal

9 Local Signaling Local signaling Target cell Secreting cell Secretory vesicle Local regulator diffuses through extracellular fluid. (a) Paracrine signaling (b) Synaptic signaling Electrical signal along nerve cell triggers release of neurotransmitter. Neurotransmitter diffuses across synapse. Target cell is stimulated. Local Regulators: work over very short distances

10 Long Distance Signaling Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream. Target cell specifically binds hormone. (c) Endocrine (hormonal) signaling Hormones are used in long- distance signaling. Both plants and animals have hormones! AKA endocrine signaling

11 The Three Stages of Cell Signaling: A Preview  Earl W. Sutherland discovered how the hormone epinephrine acts on cells  Sutherland suggested that cells receiving signals went through three processes  Reception  Transduction  Response

12 © 2011 Pearson Education, Inc. Animation: Overview of Cell Signaling Right-click slide / select “Play”

13 Reception: A cell recognizes the signal! Plasma membrane EXTRACELLULAR FLUID CYTOPLASM Reception Receptor Signaling molecule 1 What determines if a cell will respond to a signal?

14 Transduction: Converting the Signal to Action Plasma membrane EXTRACELLULAR FLUID CYTOPLASM ReceptionTransduction Receptor Signaling molecule Relay molecules in a signal transduction pathway 2 1

15 Response: Specific Cellular Action Plasma membrane EXTRACELLULAR FLUID CYTOPLASM ReceptionTransduction Response Receptor Signaling molecule Activation of cellular response Relay molecules in a signal transduction pathway 3 2 1

16 Reception: Signaling molecule and Receptor Proteins The binding between a signal molecule (ligand) and receptor is highly specific

17 Receptors in the Plasma Membrane  Most water-soluble signal molecules bind to specific sites on receptor proteins that span the plasma membrane  There are three main types of membrane receptors  G protein-coupled receptors  Receptor tyrosine kinases  Ion channel receptors

18 Type 1: G-protein Coupled Receptors  G protein-coupled receptors (GPCRs) are the largest family of cell- surface receptors  Work with the help of a G protein  The G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive G protein-coupled receptor Signaling molecule binding site Segment that interacts with G proteins

19 G-protein Function: “On” and “Off” G protein-coupled receptor Plasma membrane G protein (inactive) CYTOPLASM Enzyme Activated receptor Signaling molecule Inactive enzyme Activated enzyme Cellular response GDP GTP GDP GTP P i GDP Energy source GTP turns on the G protein GDP turns it off

20 Receptor Tyrosine Kinases  Receptor tyrosine kinases (RTKs) are membrane receptors that attach phosphates to tyrosines  A receptor tyrosine kinase can trigger multiple signal transduction pathways at once  Active form is a dimer  Abnormal functioning of RTKs is associated with many types of cancers

21 RTK – Activation Through Dimerization Signaling molecule (ligand) Ligand-binding site  helix in the membrane Tyrosines CYTOPLASM Receptor tyrosine kinase proteins (inactive monomers) Signaling molecule Dimer Tyr P P P P P P P P P P P P Activated tyrosine kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine kinase (phosphorylated dimer) Activated relay proteins Cellular response 1 Cellular response 2 Inactive relay proteins 6 ATP 6 ADP

22 Ligand-Gated Ion Channels  A ligand-gated ion channel receptor acts as a gate when the receptor changes shape  When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na + or Ca 2+, through a channel in the receptor

23 Ligand-Gated Ion Channel Activation Signaling molecule (ligand) Gate closed Ions Ligand-gated ion channel receptor Plasma membrane Gate open Cellular response Gate closed Signaling molecule binds to allow specific ions into cell These ions produce cellular responses (Ca +2 one of the most important!)

24 Intracellular Receptors: Hormones  Intracellular receptor proteins are found in the cytosol or nucleus of target cells  Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors  steroid and thyroid hormones of animals  Can act as a transcription factor, turning on specific genes

25 Hormone Activation Hormone (testosterone) Receptor protein Plasma membrane DNA NUCLEUS CYTOPLASM EXTRACELLULAR FLUID  The signaling molecule is permeable to the membrane  The receptor is found inside the cell

26 Figure Hormone (testosterone) Receptor protein Plasma membrane Hormone- receptor complex DNA NUCLEUS CYTOPLASM EXTRACELLULAR FLUID Hormone Activation  Hormone and receptor bond, activating the complex

27 Figure Hormone (testosterone) Receptor protein Plasma membrane Hormone- receptor complex DNA NUCLEUS CYTOPLASM EXTRACELLULAR FLUID Hormone Activation  One possible function of these complexes are to initiate the synthesis of specific genes  Here the complex enters the nucleus, acting as a transcription factor

28 Figure Hormone (testosterone) Receptor protein Plasma membrane Hormone- receptor complex DNA mRNA NUCLEUS CYTOPLASM EXTRACELLULAR FLUID Hormone Activation  The target RNA is made and exported for protein production

29 Figure Hormone (testosterone) Receptor protein Plasma membrane EXTRACELLULAR FLUID Hormone- receptor complex DNA mRNA NUCLEUS CYTOPLASM New protein Hormone Activation  Target protein is synthesized, completing the initial signal’s response

30 Transduction: Signal Transduction Cascades relay signals from receptors to target molecules in the cell Multistep pathways can amplify a signal and provide more opportunities for coordination and regulation of the cellular response

31 Signal Transduction Pathways  Proteins in the cytosol relay a signal from receptor  Like 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  One of the most common methods of regulating the signal is through phosphorylation and dephosphorylation

32 Protein Phosphorylation and Dephosphorylation: Molecular Switches  Protein kinases transfer phosphates from ATP to protein  phosphorylation  Protein phosphatases remove the phosphates  dephosphorylation  This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off or up or down, as required

33 Receptor Signaling molecule Activated relay molecule Phosphorylation cascade Inactive protein kinase 1 Active protein kinase 1 Active protein kinase 2 Active protein kinase 3 Inactive protein kinase 2 Inactive protein kinase 3 Inactive protein Active protein Cellular response ATP ADP ATP ADP ATP ADP PP P P P P i

34 Activated relay molecule Phosphorylation cascade Inactive protein kinase 1 Active protein kinase 1 Active protein kinase 2 Active protein kinase 3 Inactive protein kinase 2 Inactive protein kinase 3 Inactive protein Active protein ATP ADP ATP ADP ATP ADP PP P P P i P

35 Secondary Messengers: Small Molecules and Ions  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  Second messengers participate in pathways initiated by GPCRs and RTKs  Cyclic AMP and calcium ions are common second messengers

36 Cyclic AMP: Activation ATP is made into cAMP in response to an extracellular signal Adenylyl cyclase Pyrophosphate ATP P i P cAMP

37 Cyclic AMP: Regulation Phosphodiesterase AMP H2OH2O cAMP H2OH2O

38 cAMP Pathway  Many signal molecules trigger formation of cAMP  cAMP usually activates protein kinase A, which phosphorylates various other proteins  Regulation of cell metabolism is provided by G- protein systems that inhibit adenylyl cyclase G protein First messenger (signaling molecule such as epinephrine) G protein-coupled receptor Adenylyl cyclase Second messenger Cellular responses Protein kinase A GTP ATP cAMP

39 Calcium Ions  Calcium ions (Ca 2+ ) act as a second messenger in many pathways  Cells can regulate its concentration  A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol Mitochondrion EXTRACELLULAR FLUID Plasma membrane Ca 2  pump Nucleus CYTOSOL Ca 2  pump Endoplasmic reticulum (ER) ATP Low [Ca 2  ] High [Ca 2  ] Key

40 Calcium and Inositol Triphosphate  Pathways leading to the release of calcium involve inositol triphosphate (IP 3 ) and diacylglycerol (DAG) as additional second messengers

41 © 2011 Pearson Education, Inc. Animation: Signal Transduction Pathways Right-click slide / select “Play”

42 G protein EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled receptor Phospholipase C DAG PIP 2 IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) CYTOSOL Ca 2  GTP

43 G protein EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled receptor Phospholipase C DAG PIP 2 IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) CYTOSOL Ca 2  (second messenger) Ca 2  GTP

44 G protein EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled receptor Phospholipase C DAG PIP 2 IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) CYTOSOL Various proteins activated Cellular responses Ca 2  (second messenger) Ca 2  GTP

45 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”

46 Nuclear and Cytoplasmic Responses  Signal transduction pathways lead to regulation of cellular activities  The response can be cytoplasm or in the nucleus  Regulate synthesis of proteins, usually by turning genes on or off  Molecules may function as a transcription factor Growth factor Receptor Reception Transduction CYTOPLASM Response Inactive transcription factor Active transcription factor DNA NUCLEUS mRNA Gene Phosphorylation cascade P

47 Wild type (with shmoos)  Fus3  formin Mating factor activates receptor. Mating factor G protein-coupled receptor Shmoo projection forming Formin G protein binds GTP and becomes activated P P P P Formin Fus3 GDP GTP Phosphory- lation cascade Microfilament Actin subunit Phosphorylation cascade activates Fus3, which moves to plasma membrane. Fus3 phos- phorylates formin, activating it. Formin initiates growth of microfilaments that form the shmoo projections. CONCLUSION Signals Can Regulate Overall Cell Behavior

48 Fine-Tuning of the Response  There are four aspects of fine-tuning to consider  Amplification of the signal (and thus the response)  Specificity of the response  Overall efficiency of response, enhanced by scaffolding proteins  Termination of the signal

49 Fine Tuning 1 Responses: Amplification of Signal Reception Transduction Response Binding of epinephrine to G protein-coupled receptor (1 molecule) 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 ) Glycogen Glucose 1-phosphate (10 8 molecules)  Enzyme cascades amplify the cell’s response  At each step, the number of activated products is much greater than in the preceding step

50 Fine Tuning 2: The Specificity of Cell Signaling and Coordination of the Response Signaling molecule Receptor Relay molecules Response 1 Cell A. Pathway leads to a single response. Response 2Response 3 Response 4 Response 5 Activation or inhibition Cell B. Pathway branches, leading to two responses. Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.

51  Different kinds of cells have different collections of proteins  Respond to different signals  Same signal can have different effects in cells Signaling molecule Receptor Relay molecules Response 1 Cell A. Pathway leads to a single response. Response 2 Response 3 Cell B. Pathway branches, leading to two responses.

52 Response 4 Response 5 Activation or inhibition Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response. Pathway branching and “cross-talk” further help the cell coordinate incoming signals

53 Fine Tuning 3:Signaling Efficiency: Scaffolding Proteins and Signaling Complexes  Scaffolding proteins are large relay proteins to which other relay proteins are attached and can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway Signaling molecule Receptor Plasma membrane Scaffolding protein Three different protein kinases

54 Fine Tuning 4:Termination of the Signal  Inactivation mechanisms are an essential aspect of cell signaling  If ligand concentration falls, fewer receptors will be bound  Unbound receptors revert to an inactive state

55 Signal Review Reception TransductionResponse Receptor Signaling molecule Relay molecules Activation of cellular response


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