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Cell Signaling Lectures and slides with some extra things mentioned in class!

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Western University
Physiology 3140A
Jane Rylett

Cell Signaling Lecture 1 General Principles of Receptor SignalingMajor obstacle to the development of multicellular organisms was the development of a means for individual cells and tissues to communicate with each other and their environmentPurpose of cell signaling communication is to permit the development of complex mechanisms to govern behaviour of cells for the overall benefit of the organism single receptor on single cell can cause complex mechanism behavioural variationsCell Signaling Contributes toThe regulation of metabolic processesCell growth and differentiationThe integration of normal physiological responsesCombination of signals evokes different responses diagram on the leftAch has completely different effects on different cells and receptors diagrams on the rightAll living things are made of cells individual units of living matter that share the same machinery for their most basic functions Molecules Ion protein drugMolecular Machine ReceptorCell TissueOrgan SystemPerson Components of Cell Signaling1 Extracellular Signaling Molecules ligands first messengers produced by the cell to signal neighboring cells andor to regulate their own functionEither released by a cell actively and passively or expressed on the cell surface 2 Receptor Proteins bind an extracellular ligand and transduce the information provided by the signaling molecule to the inside of the cell 3 Intracellular Signaling Molecules second messengers and Signaling Proteins distribute signal to appropriate parts of the cell Intracellular signaling proteins include proteins that are protein kinases GTPbinding proteins adaptors and phosphatases 4 Target Proteins activities are altered when signaling pathway is active and changes behavior or activity of the cellAn Organized Series of Cellular Responses diagram on the left Signaling MoleculesProteins small peptides amino acids nucleotides steroid retinoids hormones lipids growth factors fatty acid derivatives ion pheromones light and dissolved gases such as NO and CO 2 Signaling Molecules are i Secreted from the signaling cell into the extracellular space by exocytosis ii Released by passive diffusion through the plasma membrane lipophylic iii Exposed to the extracellular space but remain tightly bound to the surface of the signaling cellReceptors Target cell regardless of signal responds by specific receptor protein Binding of the signaling molecule first messenger is the primary event which initiates a response in the target cell Receptor propertiesSpecificityOne receptor binds to one ligand at a timeSaturabilityLigand binding limited by number of receptors expressed on a cell Maximum response is related to number of receptors expressed 8 HighaffinityMany ligands act at very low concentrations 10M Endocrine receptors tend to have high 6affinity whereas synaptic receptors may be lower affinity 10M but are still highly specificThe way in which each cell responds to its environment varies i Receptor ExpressionComplement Set of receptors expressed by cell will determine its response ii Intracellular Machinery Depending on the intracellular machinery available to integrate and interpret the info the cell receives eg the complement of kinases ion channels phosphatases etc iii Ligand TargetsReceptor Specificity A single ligand can produce different physiological effects on different target cells by binding to multiple receptors that are coupled to distinct effector pathways or by binding to distinct receptor subtypes ex Achdifferential expression of target proteinsAcetylcholinerefer to previous diagrams a and c 1 Decrease rate and force of contraction of heart muscle mAChR G coupled 2 Stimulates skeletal muscle contraction nAChR ion channelndNote Different receptors and 2 messengersClasses of Receptors 1 Intracellular ReceptorsCytosolicnuclear steroid receptors bind to hydrophobic ligandsMany diverse ligands but have similar mechanism of action leading to the activation and direct regulation of transcription of specific genes
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