Ca(2+)-calmodulin regulated effectors of microtubule stability in neuronal tissues.
In general, microtubules are labile structures which depolymerize at low temperature and are sensitive to Ca2+. However, in brain tissue, axonal microtubules are disassembly-resistant and can exist without attachment to a microtubule organizing center. Stable microtubules cannot be purified by usual recycling procedures and this has made the elucidation of the molecular mechanisms involved in their stabilization difficult. This paper summarizes previous work in our laboratories, aimed at the identification of brain microtubule stabilizing proteins. We present assay methods which allow the detection of microtubule stability effectors in complex extracts and in chromatographic column fractions. Applied to brain crude extracts, they result in the isolation of Ca(2+)-calmodulin binding and Ca(2+)-calmodulin regulated proteins. One, called STOP, appears to account for microtubule stabilization in neurons. A second protein with similar activity is myelin basic protein. Non-neuronal tissues also contain Ca(2+)-calmodulin-regulated effectors which appear to differ in structure from their neuronal counterparts. Thus, in all tissues examined, microtubule stability seems to be accounted for by unique Ca(2+)-calmodulin regulated proteins, showing tissue specificity.
Pirollet
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Département de Biologie Moléculaire et Structurale, INSERM U244, Centre d'Etudes Nucléaires de Grenoble, France.
Margolis
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RL
Job
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D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002118:Calcium / Q000494:pharmacology*; D002147:Calmodulin / Q000494:pharmacology*; D002417:Cattle; D008868:Microtubule Proteins / Q000032:analysis* / Q000302:isolation & purification; D008869:Microtubule-Associated Proteins / Q000032:analysis* / Q000302:isolation & purification; D008870:Microtubules / Q000187:drug effects*; D014020:Tissue Extracts / Q000737:chemistry
D002147:Calmodulin; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; D014020:Tissue Extracts; D002118:Calcium