Signalling Mechanisms Themba Hospital FCOG(SA) Part 1 Tutorials By Dr N.E Manana
Background Cells depend on signalling systems to adapt to changing environmental conditions. Free-living organisms , respond to changes in temperature , osmotic stress , and nutrients by synthesizing the proteins required to their survival Motile cells respond to chemicals by migrating toward attractants and away from repellents Main molecular components of signalling pathways: receptors , protein messengers , and second messengers
Receptors vs Stimuli Cells use molecular receptors to detect chemical and physical stimuli . Physical interaction of the stimulus with the receptor provides energy to modify the structure of the receptor and initiate a signalling pathway With the exception of RNA “riboswitches,” all receptors are proteins A few stimuli , including light, steroid hormones , and gases, penetrate the plasma membrane and react with receptors inside the cell
Receptors vs Stimuli Active receptors generate a chemical sig nal inside the cell by interacting with one or more cytoplasmic proteins This transduction step converts one type of signal ( the stimulus ) into another signal ( the messenger ) and often amplifies the signal The cytoplasmic domains of active seven-helix receptors catalyze the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP) on signal-transducing guanosine triphosphatases (GTPases), called G-proteins . GTP binding activates t hese G-proteins , allowing them to bind and regulate target proteins .
Second Messengers These second messengers are chemically diverse, ranging from hydrophobic lipids confined to membrane bilayers , to an inorganic ion ( Ca2+ ), to nucleotides ( [ cAMP ] and [ cGMP ]), to a gas ( nitric oxide ) They modify cellular behaviou r by binding to and activating a wide range of effector proteins , regulating membrane physiology , cellular metabolism , motility , and gene expression . Effector systems include transcription factors
Calcium Signalling Calcium ion , Ca2+ , is a versatile second messenger that regulates many processes , including synaptic transmission , fertilization , secretion , muscle contraction, and cytokinesis . Ca2+ is released into and removed from the cytoplasm ATP-driven Ca2+ pumps in the plasma membrane and ER keep cytoplasmic Ca2+ levels low A variety of stimuli , operating through different receptors open Ca2+ channels , allowing a concentrated burst of Ca2+ to enter the cytoplasm
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Biochemical approach Identification of a naturally occurring or synthetic chemical, that modify the activity of an organism , organ , or cell These compounds are called agonists, effects of agonists are often aided by the discovery of antagonists Antagonists prove to be useful as drugs