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Cell signaling
- 1. CELL SIGNALING LIVING CELLS SAY: CAN YOU HEAR ME NOW? TU ANH TRAN HPS 730 â RADIATION BIOLOGY FALL 2013 UNLV
- 2. TABLE OF CONTENT ⢠Cell Signaling ⢠Signaling Modes ⢠Response Time ⢠Response Variance ⢠Receptor Proteins ⢠Molecular Switches ⢠Intracellular Mechanisms ⢠Cell Sensitization http://web.mit.edu/newsoffice/2011/cell-signaling-received-1117.html
- 3. Cell signaling ⢠Unicellular organisms: quorum sensing ⢠Increase in concentration as population density increases ⢠Bacteria ⢠Chemical signals secreted from neighbors ⢠Coordination of behaviors ⢠Motility, antibiotic production, spore formation, sexual conjugation ⢠Multicellular organisms: elaborate signaling systems ⢠Human genome: over 1500 genes that encode receptor proteins ⢠RNA splicing and post-transcriptional modifications ⢠Small protein family groups
- 4. ⢠Extracellular signal molecules ⢠long distance ⢠Immediate proximity ⢠Intracellular signaling pathways ⢠Receptor proteins ⢠Effector proteins ⢠Metabolic enzyme ⢠Alter metabolism ⢠Gene regulatory proteins ⢠Alter gene expression ⢠DNA synthesis ⢠Cytoskeletal proteins ⢠Alter cell shape or movement
- 5. ⢠Contact-dependent signaling â direct membrane to membrane contact ⢠Signal molecules ⢠Bound to the surface of the signaling cell ⢠Influence cells that come in contact ⢠Paracrine signaling ⢠Long ranged ⢠Short ranged ⢠Act as local mediator ⢠Autocrine signaling ⢠Cancer cells ⢠Self-signaling ⢠Survival ⢠Proliferation Signaling Modes
- 6. Signaling Modes ⢠Synaptic signaling - long-range ⢠Neurons â neurotransmitters ⢠Axons - electrical impulses, chemical synapses ⢠Endocrine signaling â long range ⢠Hormones
- 7. Signaling Modes ⢠Gap junctions ⢠Allow neighboring cells to share information ⢠Water-filled channels ⢠Exchange of inorganic ions and small water-soluble molecules ⢠Bypass the plasma membranes ⢠Information passing in both directions
- 8. Time
- 9. Response Variance ⢠Each cell is programmed to respond to specific combinations of extracellular signal molecules ⢠Survive ⢠Grow and divide ⢠Differentiate ⢠Die ⢠Same signal molecules can activate different responses in different types of cells ⢠Heart muscle cell â decrease rate and force of contraction ⢠Salivary gland cell - secretion
- 10. Receptor Proteins ⢠Signaling cells ⢠Signal molecules ⢠Released into extracellular space via exocytosis ⢠Hydrophobic ⢠Proteins ⢠Small peptides ⢠Amino acids ⢠Nucleotides ⢠Steroids ⢠Retinoids ⢠Fatty acid derivatives ⢠Dissolved gases ⢠Nitric oxide ⢠Carbon monoxide ⢠Target cells ⢠Receptor ⢠Binds the signal molecules ⢠Initiates response ⢠Generate intracellular signals
- 11. Three Families of Cell-Surface Receptors ⢠Ion-channel-coupled receptors â rapid synaptic signaling ⢠Trasmitter-gated ion channels ⢠Open or close briefly in response to the binding of a neutrotransmitter ⢠G-protein-coupled receptors ⢠Indirectly activiate/deactivate plasma-membrane-bound enzymes or ion channels ⢠Enzyme-coupled receptors ⢠Enzymes or protein kinases that phosphorylate the receptors and proteins within the target cell ⢠Receptors involved in proteolysis ⢠Tissue renewal and repair
- 15. Intracellular Signaling Proteins As Molecular Switches ⢠Phosphorylation ⢠Protein kinases ⢠Add or remove a phosphate group ⢠GTP-binding proteins or G-proteins ⢠GTP â on ⢠GDP - off
- 16. Intracellular Mechanisms ⢠Feedback loops ⢠Positive feedback loops ⢠Depend on the strength of the feedback ⢠Moderate: increase the response to the signal ⢠Strong: increase in the quantity of product ⢠Have lasting effect ⢠Delay negative feedback loops ⢠Counter the effect of a stimulus ⢠Produce responses that oscillate depending on the environment ⢠Allow cells to adapt
- 17. Feedback Loop â An Example http://ajpcell.physiology.org/content/282/3/C545
- 18. Cell Sensitization To Signals ⢠Cells can be desensitized to a prolonged exposure to a stimulus ⢠While a stimulus persist, a sudden increase can stimulate the signal again.
- 19. References ⢠Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Extracellular Control of Cell Division, Cell Growth, and Apoptosis. ⢠http://web.mit.edu/newsoffice/2011/cell-signaling-received-1117.html ⢠http://ajpcell.physiology.org/content/282/3/C545
Notas do Editor
- -Allow for coordination of behavior, motility, antibiotic production, spore formation and sexual conjugation-The number of different receptor proteins is further increased by alternative RNA splicing and post-translational modifications. -All of the proteins can be divided into small family groups with the few exceptions that do not belong in any of these 3 protein classes.
- The signal molecule usually binds to a receptor protein that is embedded in the plasma membrane of the target cell and activates one or more intracellular signaling pathways The intracellular signaling proteins alter the activity of effector proteins and thereby the behavior of the cell.
- -For paracrine signals to act only locally, the secreted molecules must not be allowed to diffuse too far; for this reason they are often rapidly taken up by neighboring target cells, destroyed by extracellular enzymes, or immobilized by the extracellular matrix.
- (C) Synaptic signaling is performed by neurons that transmit signals electrically along their axons and release neurotransmitters at synapses, which are often located far away from the neuronal cell body-. (D) Endocrine signaling depends on endocrine cells, which secrete hormones into the bloodstream for distribution throughout the body. Many of the same types of signaling molecules are used in paracrine, synaptic, and endocrine signaling; the crucial differences lie in the speed and selectivity IN which the signals are delivered to their targets.
- The speed of a response to an extracellular signal depends not only on the mechanism of signal delivery but also on the nature of the target cellâs response. When the response requires only changes in proteins already present in the cell such as responses that depend solely on protein phosphorylation can occur within seconds. -When the response involves changes in gene expression and the synthesis of new proteins, however, it usually requires many minutes or hours, regardless of the mode of signal delivery
- -the receptor proteins are inside the target cell, and the signal molecule has to enter the cell to bind to them: this requires that the signal molecule be sufficiently small and hydrophobic to diffuse across the target cellâs plasma membrane
- Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids.
- guanosine triphosphate
- -A positive feedback can have a lasting effect well beyond the lifetime of the signaling molecules