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Cell communication
- 1. Cell CommuniCation Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 2. Overview: The Cellular Internet • Cell-to-cell communication is essential for multicellular organisms • Biologists have discovered some universal mechanisms of cellular regulation Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 3. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 4. External signals are converted into responses within the cell • Microbes are a window on the role of cell signaling in the evolution of life Are similar in microbes and mammals, suggesting an Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings early origin
- 5. Evolution of Cell Signaling • 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 • Signal transduction pathways convert signals on a cell’s surface into cellular responses • Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and have since been adopted by eukaryotes Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 6. Exchange of mating factors Mating Receptor a factor a a Yeast cell, a factor mating type a Yeast cell, mating type a a a a/a New a/a cell
- 7. 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 8. Plasma membranes Gap junctions between animal cells Cell junctions Cell-cell recognition Plasmodesmata between plant cells
- 9. • 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 10. Local regulator diffuses through extracellular fluid Paracrine signaling Local signaling Secretory vesicle Secreting cell Target cell Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell is stimulated Synaptic signaling Target cell Hormonal 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 12. LE 11-5_1 EXTRACELLULAR FLUID Reception Plasma membrane Transduction CYTOPLASM Receptor Signal molecule
- 13. EXTRACELLULAR FLUID Reception Plasma membrane Transduction CYTOPLASM Receptor Signal molecule Relay molecules in a signal transduction pathway
- 14. EXTRACELLULAR FLUID Reception Plasma membrane Transduction CYTOPLASM Receptor Signal molecule Relay molecules in a signal transduction pathway Response Activation of cellular response
- 15. 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 16. 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 17. 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. NUCLEUS CYTOPLASM DNA Hormone (testosterone) Receptor protein Hormone-receptor complex mRNA New protein
- 18. 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 19. • 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 20. Signal-binding site Segment that interacts with G proteins G-protein-linked receptor
- 21. • Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines • A receptor tyrosine kinase can trigger multiple signal transduction pathways at once Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 22. Signal molecule a Helix in the membrane Signal-binding site Tyr Tyrosines Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins CYTOPLASM (inactive monomers) Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr ATP 6 ADP Activated tyrosine-kinase regions (unphosphorylated dimer) Signal molecule Dimer Tyr PP P Tyr Tyr Tyr Tyr Tyr PPP Fully activated receptor tyrosine-kinase (phosphorylated dimer) P Tyr Tyr Tyr Tyr Tyr Tyr PP PPP Activated relay proteins Inactive relay proteins Cellular response 1 Cellular response 2 6
- 23. • 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 24. Signal molecule (ligand) Gate closed Ions Ligand-gated ion channel receptor Plasma membrane Gate closed Gate open Cellular response
- 25. 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 26. 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 27. Protein Phosphorylation and Dephosphorylation • In many pathways, the signal is transmitted by a cascade of protein phosphorylations • Phosphatase enzymes remove the phosphates • This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 28. 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 Pi ADP ATP PP Pi ADP ATP PP Pi P P P
- 29. 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 30. 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 31. Adenylyl cyclase Pyrophosphate P Pi Phosphodiesterase H2O ATP Cyclic AMP AMP
- 32. • 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 33. 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
- 34. 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 35. EXTRACELLULAR FLUID ATP ATP Ca2+ pump Mitochondrion Plasma membrane CYTOSOL Endoplasmic reticulum (ER) Ca2+ pump Nucleus Ca2+ pump Key High [Ca2+] Low [Ca2+]
- 36. • 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 Animation: Signal TTrraannssdduuccttiioonn PPaatthhwwaayyss Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 37. EXTRACELLULAR FLUID Endoplasmic Ca2+ reticulum (ER) CYTOSOL Signal molecule (first messenger) G protein GTP IP3-gated calcium channel DAG IP3 (second messenger) G-protein-linked PIP2 receptor Phospholipase C
- 38. EXTRACELLULAR FLUID Endoplasmic Ca2+ reticulum (ER) CYTOSOL Signal molecule (first messenger) G protein GTP IP3-gated calcium channel DAG IP3 (second messenger) G-protein-linked PIP2 receptor Phospholipase C Ca2+ (second messenger)
- 39. EXTRACELLULAR FLUID Endoplasmic Ca2+ reticulum (ER) CYTOSOL Signal molecule (first messenger) G protein GTP IP3-gated calcium channel DAG IP3 (second messenger) G-protein-linked PIP2 receptor Phospholipase C Ca2+ (second messenger) Various proteins activated Cellular re-sponses
- 40. Response: Cell signaling leads to regulation of cytoplasmic activities or transcription • The cell’s response to an extracellular signal is sometimes called the “output response” Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 41. 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 42. 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) Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Glycogen Response Glucose-1-phosphate (108 molecules)
- 43. • 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 44. Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor P Response Gene mRNA DNA NUCLEUS
- 45. 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 © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 46. 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 © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 47. 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 48. Signal molecule Receptor Relay molecules Response 1 Response 2 Response 3 Cell B. Pathway branches, leading to two responses Cell A. Pathway leads to a single response Activation or inhibition Response 4 Response 5 Cell C. Cross-talk occurs between two pathways Cell D. Different receptor leads to a different response
- 49. 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 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
- 50. LE 11-16 Signal molecule Plasma membrane Receptor Scaffolding protein Three different protein kinases
- 51. 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 • http://www.wiley.com/college/boyer/0470003790/animations/• https://www.youtube.com/watch?v=wC2_7Ror3qY Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings