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Chapter 11

11.2 Reception: A signaling molecule binds to a receptor protein, causing it to change shape. 11.1 external signals Are converted to responses within. 11.3 Transduction: Cascades of molecular Interactions relay signals from receptors to cells. 11.4

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Chapter 11

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  1. 11.2 Reception: A signaling molecule binds to a receptor protein, causing it to change shape 11.1 external signals Are converted to responses within 11.3 Transduction: Cascades of molecular Interactions relay signals from receptors to cells 11.4 Response: Cell signaling leads to regulation of transcription or cytoplasmic activities 11.5 Apoptosis integrates multiple cell-signaling pathways. Chapter 11 Cell signaling and communication

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

  3. a factor Exchange of mating factors Receptor a a a factor Yeast cell, mating type a Yeast cell, mating type a Mating a a LE 11-2 New a/a cell a/a

  4. 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

  5. Plasma membranes Plasmodesmata between plant cells Gap junctions between animal cells Cell junctions LE11-3 Cell-cell recognition

  6. Local signaling Long-distance signaling Target cell Endocrine cell Blood vessel Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Secreting cell Secretory vesicle Hormone travels in bloodstream to target cells Local regulator diffuses through extracellular fluid Target cell Target cell is stimulated Paracrine signaling Synaptic signaling LE 11-4 Hormonal signaling

  7. 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

  8. EXTRACELLULAR FLUID CYTOPLASM Plasma membrane Reception Transduction Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signal molecule LE 11-5_3

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

  10. 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

  11. Hormone (testosterone) EXTRACELLULAR FLUID The steroid hormone testosterone passes through the plasma membrane. Plasma membrane Testosterone binds to a receptor protein in the cytoplasm, activating it. Receptor protein Hormone- receptor complex The hormone- receptor complex enters the nucleus and binds to specific genes. DNA The bound protein stimulates the transcription of the gene into mRNA. mRNA LE 11-6 NUCLEUS New protein The mRNA is translated into a specific protein. CYTOPLASM

  12. 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

  13. 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

  14. Signal-binding site Segment that interacts with G proteins LE 11-7aa G-protein-linked receptor

  15. 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.

  16. Signal molecule Signal-binding site a Helix in the membrane Signal molecule Tyr Tyr Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins (inactive monomers) Dimer CYTOPLASM Activated relay proteins Cellular response 1 P P Tyr Tyr P Tyr Tyr Tyr Tyr P P P Tyr Tyr P Tyr Tyr Tyr Tyr P LE 11-7b P P Cellular response 2 Tyr Tyr P Tyr Tyr Tyr P Tyr 6 ATP 6 ADP Activated tyrosine- kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine-kinase (phosphorylated dimer) Inactive relay proteins

  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 Ca2+, through a channel in the receptor

  18. Gate closed Signal molecule (ligand) Ions Plasma membrane Ligand-gated ion channel receptor Gate open Cellular response LE 11-7c Gate closed

  19. Concept 11.3: 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 (phosphotases) system acts as a molecular switch, turning activities on and off

  22. Signal molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP ADP P Active protein kinase 2 Phosphorylation cascade PP P i Inactive protein kinase 3 ATP ADP P Active protein kinase 3 LE 11-8 PP P i Inactive protein ATP P ADP Cellular response Active protein PP P i

  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[adenosine monophosphate (adenylic acid)] • 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. Phosphodiesterase Adenylyl cyclase Pyrophosphate H2O P P i ATP Cyclic AMP AMP LE 11-9

  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. First messenger (signal molecule such as epinephrine) Adenylyl cyclase G protein G-protein-linked receptor GTP ATP Second messenger cAMP Protein kinase A LE 11-10 Cellular responses

  28. Calcium ions and Inositol Triphosphate (IP3) • Calcium ions (Ca2+) act as a second messenger in many pathways • Calcium is an important second messenger because cells can regulate its concentration

  29. EXTRACELLULAR FLUID Plasma membrane Ca2+ pump ATP Mitochondrion Nucleus CYTOSOL Ca2+ pump LE 11-11 Endoplasmic reticulum (ER) ATP Ca2+ pump Low [Ca2+] High [Ca2+] Key

  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 (IP3) and diacylglycerol (DAG) as second messengers

  31. EXTRACELLULAR FLUID Signal molecule (first messenger) G protein DAG GTP G-protein-linked receptor PIP2 Phospholipase C IP3 (second messenger) IP3-gated calcium channel LE 11-12_3 Cellular re- sponses Various proteins activated Endoplasmic reticulum (ER) Ca2+ Ca2+ (second messenger) CYTOSOL

  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. Reception Binding of epinephrine to G-protein-linked 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) Inactive phosphorylase kinase Active phosphorylase kinase (105) LE 11-13 Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Response Glycogen Glucose-1-phosphate (108 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. Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor Response LE 11-14 P DNA Gene NUCLEUS mRNA

  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 2 Response 3 Response 1 Cell A. Pathway leads to a single response Cell B. Pathway branches, leading to two responses LE 11-15 Activation or inhibition Response 5 Response 4 Cell D. Different receptor leads to a different response Cell C. Cross-talk occurs between two pathways

  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. LE 11-16 Signal molecule Plasma membrane Receptor Three different protein kinases Scaffolding protein

  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

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