Cellular Signaling / Signal Transduction PDF

Biology 1310 - Genes, Cells and Macromolecules Cellular signalling / signal transduction The readings for this topic are pages 222 to 236 in Campbell Biology: 3rd Canadian Edition. An important part of cell function is their ability to communicate with each other. E...

Biology 1310 - Genes, Cells and Macromolecules Cellular signalling / signal transduction The readings for this topic are pages 222 to 236 in Campbell Biology: 3rd Canadian Edition. An important part of cell function is their ability to communicate with each other. Exchanging key molecules directly (Fig. 11.4) - gap junctions; animal cells - plasmodesmata; plant cells Cell-cell recognition - surface ligands on one cell bind to surface receptors on the other cell, target cell will respond Cellular communication by released molecular signals - yeast cells have two mating types ("A" and "alpha") for the purposes of sexual recombination (Fig. 11.2) - "A" cells release the "A" mating factor, for which "alpha" cells have a receptor - "alpha" cells release the "alpha" mating factor, for which "A" cells have a receptor - when haploid yeast cells receive the mating factor of the other type, the cells can fuse to form a diploid, and enter meiosis and genetic recombination Under conditions of nutrient scarcity, Myxococcus bacteria in the soil can collectively form a structure that will allow for the production of resistant spores that will survive the environmental challenges. (Fig. 11.3) - specialized colony is a result of released chemical signals that each individual cell can recognize. - many single celled eukaryotes can do the same sort of thing. A tremendously important part of the function of the membrane is to receive and/or absorb appropriate chemical messengers from outside the cell. These chemical messengers cause an alteration in the way the cell functions or the way that genes are expressed (signal transduction). Such signalling between cells is absolutely critical to the integrity and functioning of multi-cellular organisms. Signals released by other cells are typically bound to an appropriate trans-membrane receptor protein (Fig. 11.6) - Not all cells, only the appropriate target ones, have the receptor protein - binding between the signal (ligand) and the receptor is generally very specific Ligand binding (reception) will cause a change in shape of the receptor, which then will interact with molecules inside the cell to indicate that a signal has been received (signal transduction). The cell will respond to that signal in the appropriate way. Signals can be carried over short or long distances (Fig. 11.5) Short - Pararcine: local regulators (e.g. growth factors) - Synaptic (e.g. acetylcholine) Long - Endocrine (e.g. hormones) Many ligand-receptor complexes activate G-proteins inside the cell, and are thus known as G protein- coupled receptors (GPCR). (Fig. 11.8) -typically comprised of a series of alpha-helix transmembrane protein domains (Fig. 11.7) - causes GTP to bind to the G-protein; these will then activate an enzyme, using the energy in the GTP to do so - e.g. growth factors, epinephrine - key in such important functions as embryonic development and sensory reception (taste, smell, vision) - many infectious agents interfere with G-protein related pathways; consequently, many conventional medicines attempt to deal with these interferences - e.g. opioids (such as morphine, oxycodone) Other types of signal transduction receptors can mediate a number of processes at once. The receptor tyrosine kinases are a key example of this. (Fig. 11.8) - Kinases are enzymes that catalyze the transfer of phosphate groups between macromolecules. - Receptor tyrosine kinases are transmembrane proteins that have, on the outside of the cell, ligand binding site for a particular signaling molecule, and on the inside of the cell, have tyrosine kinase functions with specific tyrosine portions that can be phosphorylated. - When the signaling ligand binds to two such protein monomers in the membrane, they will come together to form a dimeric protein. This activates the tyrosine kinase activity of the protein, and the exposed tyrosine amino acids will then phosphorylate. - Once phosphorylated, the tyrosines can bind to relay proteins, thus activating them, and initiating whatever cellular response they are responsible for. - Disruptions to tyrosine kinase mediated pathways are involved in a number of cancers in humans. Other receptor proteins allow ions to flow into a cell when bound to a ligand (ligand-gated ion channel) (Fig. 11.8) - e.g. nerve cells, in response to neurotransmitter proteins In some cases, the signal molecule is hydophobic and can traverse the membrane. In such cases, the receptor molecule is inside the cell (Fig. 11.9) - e.g. steroid-based hormones such as testosterone - steroid-receptor complexes typically act as transcription factors Signal transduction typically works through as a cascade, whereby many proteins are activated in sequence (Fig. 11.10) - this enhances the effect of a small number of signalling molecules - cascading molecules often a series of protein kinases, the last of which activates (by phosphorylation) the protein meant to give the appropriate cellular response. (Fig. 11.15) - protein kinases deactivated by protein phosphatases. These various aspects of cellular signalling do not work in isolation. The ras oncogene is a good example (Fig. 18.24) - growth factor activates tyrosine kinase, which then activates ‘ras’ protein (itself a G-protein), which then activates a protein kinase cascade, which then activates a transcription factor for a gene promoting cell growth. - a mutation in the gene for ‘ras” means that the ras protein is activated, even when there is no growth factor binding the tyrosine kinase. Cell growth an proliferation goes on, even when it shouldn’t Some signal transduction pathways use non-protein intermediates, or “second messengers” - diffuse fast, and so work very quickly to activate other molecules - especially calcium ion (Ca+2) and cyclic AMP (cAMP) (Fig. 11.11) - many cyclic AMP formed from ATP by G-protein activated adenylyl cyclase (Fig. 11.12) - cAMP then activates protein kinase A, which then phosphorylates target proteins - calcium is normally in low concentration in the cytoplasm - additional calcium can be released into the cytoplasm from the endoplasmic reticulum in response to activation of either G-proteins or tyrosine kinase receptors. (Fig. 11.14) - raised calcium level can induce a number of changes within the cell - sarcoplasmic reticulum in muscle cells. More often than not, the ultimate goal of signal transduction is alteration to expression of certain genes (Fig. 11.15) -------------------------------------------------- Mastering Biology Study Area For more detail on the specific issues concerning cellular membranes, watch the following animations: - Chapter 11: Overview of Cell Signaling - Chapter 11: Reception - Chapter 11: Signal Transduction Pathways - Chapter 11: Nuclear Response: Activating a Gene - Chapter 11: Cytoplasmic Response: Glycogen Breakdown - Chapter 11: Mechanism of Hormone Action: Second Messenger cAMP