Microtubules exhibit equilibrium and treadmilling reactions which may be integral to many of their cytoplasmic functions. Understanding the physiological regulation of the microtubule steady state is therefore arguably of paramount importance to our understanding of the molecular mechanisms of microtubule behavior. We propose to further study one regulatory system which profoundly affects microtubule stability and equilibrium behavior. In the presence of substoichiometric amounts of a regulatory factor, microtubules become extremely stable to millimolar calcium, to cold temperature and to assembly inhibiting drugs. These microtubules are referred to as """"""""cold stable."""""""" The cold stable microtubule regulatory material in turn is apparently subject to control mechanisms, losing its activity when exposed to Ca++ calmodulin or upon phosphorylation. We have isolated a discrete polypeptide complex which contains the stabilizing activity, and we propose to use biochemical and cell biological approaches to characterize the mechanisms by which it regulates microtubule equilibria. Our major goals are presently to determine the parameters that regulate the interaction of this complex with microtubules, to determine if it contains active subcomponents, and to determine if this complex represents a microtubule regulatory mechanism common to many cell types. Our overall goal is to determine how such a regulatory mechanism can serve to integrate microtubule behavior into the overall physiological response of cells to calmodulin and kinase activating stimuli.
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