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The Cellular Internet Cell-to-cell communication is essential for multicellular organisms Biologists have discovered some universal mechanisms of cellular.

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Presentation on theme: "The Cellular Internet Cell-to-cell communication is essential for multicellular organisms Biologists have discovered some universal mechanisms of cellular."— Presentation transcript:

1 The Cellular Internet Cell-to-cell communication is essential for multicellular organisms Biologists have discovered some universal mechanisms of cellular regulation

2 Exchange of mating factors Mating Receptor a   factor a  a factor Yeast cell, mating type a Yeast cell, mating type  a/  New a/  cell

3 Local and Long-Distance Signaling Cells in a multicellular organisms 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 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

4 Plasma membranes Gap junctions between animal cells Cell junctions Cell-cell recognition Plasmodesmata between plant cells

5 Paracrine signaling Local regulator diffuses through extracellular fluid Secretory vesicle Secreting cell Target cell Local signaling Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Endocrine cell Blood vessel Long-distance signaling Hormone travels in bloodstream to target cells Synaptic signaling Target cell is stimulated Hormonal signaling Target cell

6 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 3 processes: – Reception – Transduction – Response

7 EXTRACELLULAR FLUID Reception Plasma membrane Transduction CYTOPLASM Receptor Signal molecule Relay molecules in a signal transduction pathway Response Activation of cellular response

8 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 conformational change in a receptor is often the initial transduction of the signal Most signal receptors are plasma membrane proteins

9 Intracellular Receptors Some receptor proteins are intracellular, found in the cytosol or nucleus of target cells Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors Examples of hydrophobic messengers are the steroid and thyroid hormones of animals An activated hormone-receptor complex can act as a transcription factor, turning on specific genes

10 EXTRACELLULAR FLUID Plasma membrane The steroid hormone testosterone passes through the plasma membrane. Testosterone binds to a receptor protein in the cytoplasm, activating it. The hormone- receptor complex enters the nucleus and binds to specific genes. The bound protein stimulates the transcription of the gene into mRNA. The mRNA is translated into a specific protein. CYTOPLASM NUCLEUS DNA Hormone (testosterone) Receptor protein Hormone- receptor complex mRNA New protein

11 Receptors in the Plasma Membrane 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-linked receptors – Receptor tyrosine kinases – Ion channel receptors

12 A G-protein-linked receptor is a plasma membrane receptor that works 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

13 Segment that interacts with G proteins Signal-binding site G-protein-linked receptor

14 Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines A receptor tyrosine kinase can trigger multiple signal transduction pathways at once A kinase, alternatively known as a phosphotransferase, is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates. The process is referred to as phosphorylation.kinaseenzymephosphatehigh-energyATP substrates phosphorylation

15 Signal molecule  Helix in the membrane Signal-binding site Tyr Tyrosines Receptor tyrosine kinase proteins (inactive monomers) CYTOPLASM Tyr Activated tyrosine- kinase regions (unphosphorylated dimer) Signal molecule Dimer Fully activated receptor tyrosine-kinase (phosphorylated dimer) Tyr P P P P P P ATP 6 ADP Tyr P P P P P P Inactive relay proteins Cellular response 2 Cellular response 1 Activated relay proteins 6


17 An 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

18 Signal molecule (ligand) Gate closed Ions Ligand-gated ion channel receptor Plasma membrane Gate closed Gate open Cellular response

19 Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell 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

20 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 conformational change

21 Protein Phosphorylation and Dephosphorylation In many pathways, the signal is transmitted by a cascade of protein phosphorylations Phosphatase enzymes remove the phosphates This phosphorylation (kinases) and dephosphorylation (phosphatases) system acts as a molecular switch, turning activities on and off

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

23 Small Molecules and Ions as Second Messengers Second messengers are small, nonprotein, water-soluble molecules or ions The extracellular signal molecule that binds to the membrane is a pathway’s “first messenger” Second messengers can readily spread throughout cells by diffusion Second messengers participate in pathways initiated by G-protein-linked receptors and receptor tyrosine kinases

24 Cyclic AMP Cyclic AMP (cAMP) is 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

25 ATPCyclic AMPAMP Adenylyl cyclase Pyrophosphate PP i Phosphodiesterase H2OH2O

26 Many signal molecules trigger formation of cAMP Other components of cAMP pathways are G proteins, G-protein-linked receptors, and protein kinases 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

27 cAMP ATP Second messenger First messenger (signal molecule such as epinephrine) G-protein-linked receptor G protein Adenylyl cyclase Protein kinase A Cellular responses GTP

28 Calcium ions and Inositol Triphosphate (IP 3 ) Calcium ions (Ca 2+ ) act as a second messenger in many pathways Calcium is an important second messenger because cells can regulate its concentration

29 ATP EXTRACELLULAR FLUID ATP Mitochondrion Ca 2+ pump Plasma membrane CYTOSOL Endoplasmic reticulum (ER) Ca 2+ pump Ca 2+ pump High [Ca 2+ ] Key Nucleus Low [Ca 2+ ]

30 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 second messengers

31 CYTOSOL Ca 2+ Endoplasmic reticulum (ER) IP 3 -gated calcium channel IP 3 (second messenger) DAG PIP 2 G-protein-linked receptor Phospholipase C G protein Signal molecule (first messenger) EXTRACELLULAR FLUID GTP Ca 2+ (second messenger) Various proteins activated Cellular re- sponses

32 Cytoplasmic and Nuclear Responses Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities The response may occur in the cytoplasm or may involve action in the nucleus Many pathways regulate the activity of enzymes

33 Binding of epinephrine to G-protein-linked receptor (1 molecule) Reception 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 Inactive phosphorylase kinase Active protein kinase A (10 4 ) Active phosphorylase kinase (10 5 ) Active glycogen phosphorylase (10 6 ) Inactive glycogen phosphorylase Glycogen Response Glucose-1-phosphate (10 8 molecules)

34 Many other 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

35 Reception Growth factor Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor P Response Gene mRNA DNA NUCLEUS

36 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

37 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

38 The Specificity of Cell Signaling Different kinds of cells have different collections of proteins These differences in proteins give each kind of cell specificity in detecting and responding to signals The response of a cell to a signal depends on the cell’s particular collection of proteins Pathway branching and “cross-talk” further help the cell coordinate incoming signals

39 Signal molecule Receptor Relay molecules Response 1 Response 2Response 3 Cell B. Pathway branches, leading to two responses Cell A. Pathway leads to a single response Cell C. Cross-talk occurs between two pathways Response 4 Response 5 Activation or inhibition Cell D. Different receptor leads to a different response

40 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

41 Signal molecule Plasma membrane Receptor Scaffolding protein Three different protein kinases

42 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

43 Animations and Videos Biomembranes II: Membrane Dynamics and CommunicationBiomembranes II: Membrane Dynamics and Communication Bozeman - Cell Communication Bozeman - Evolutionary Significance of Cell CommunicationBozeman - Evolutionary Significance of Cell Communication Cell Junctions Tight Junctions Desmosomes Gap Junctions

44 Animations and Videos Bozeman - Signal Transduction Second Messengers (cAMP and Ca+2 Pathways) Chemical Synapse – 1 Chemical Synapse – 2 Voltage-Gated Channels and the Action Potential Signal Transduction Pathway Signaling by Secreted Molecules Signal Transduction

45 Animations and Videos 2nd Messenger Signal Amplification – 1 Signal Amplification – 2 Hormonal Communication Mechanism of Steroid Hormone Action Mechanism of Thyroxine Action Action of Epinephrine on a Liver Cell Action of Glucocorticoid Hormone

46 Animations and Videos Intracellular Receptor Model Mechanism of Action of Lipid-Soluble Messengers Mechanism of Thyroxine Action Mechanism of Steroid Hormone Action Lipid Soluble Hormone Chapter Quiz Questions – 1 Chapter Quiz Questions - 2

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