Regulation of glutamate receptor binding by the cytoskeletal protein fodrin.
The erythrocyte cytoskeleton, which consists primarily of a meshwork of spectrin and actin, controls cell shape and the disposition of proteins within the membrane. Proteins similar to spectrin have recently been found in diverse cells and tissues, and it is possible that they mediate the capping of cell-surface receptors, although this has not been demonstrated directly. In neurones, the spectrin-like protein fodrin lines the cortical cytoplasm and may link actin filaments to the membrane. Fodrin has been hypothesized to regulate the number of receptor binding sites on neuronal membranes for the putative neurotransmitter L-glutamate. Micromolar calcium concentrations activate the thiol protease calpain I, induce fodrin degradation and more than double the density of glutamate binding sites; these effects are all blocked by thiol protease inhibitors. We have now used specific antibodies to examine further the role of fodrin proteolysis in regulating glutamate receptors. We report that fodrin antibodies block the fodrin degradation and increase in glutamate binding normally induced by calcium, and so provide direct evidence for control of membrane receptors by a non-erythroid spectrin.
Siman
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Baudry
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Lynch
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D000818:Animals; D001921:Brain / Q000502:physiology; D002118:Calcium / Q000502:physiology; D002154:Calpain; D002352:Carrier Proteins / Q000276:immunology / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000276:immunology / Q000502:physiology*; D010450:Endopeptidases / Q000502:physiology*; D018260:Gelsolin; D008840:Microfilament Proteins / Q000276:immunology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology; D009474:Neurons / Q000502:physiology; D051381:Rats; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013049:Spectrin
D002118:Calcium; D002154:Calpain; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D010450:Endopeptidases; D018260:Gelsolin; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D013049:Spectrin; C016953:brevin