Altered expression of a heat shock protein in the mammalian nervous system in the presence of agents which affect microtubule stability.

In vitro incubation of the isolated rabbit retina at elevated temperature results in the synthesis of a heat shock protein of M.W. 74,000 (hsp74). Recently we have demonstrated that this protein is associated with preparations of purified retinal microtubules and intermediate filaments. In order to examine the possibility that hsp74 synthesis is related to cytoskeletal stability, the effects of agents known to specifically affect microtubules were examined using an in vitro retinal system. Taxol, an antimitotic agent which stabilizes microtubules, was found to reduce the level of hsp74 synthesized in response to elevated temperature. Colchicine, a potent microtubule de-stabilizing agent, did not induce hsp74 synthesis in the absence of elevated temperature, however, under heat shock conditions, hsp74 synthesis was elevated in the presence of colchicine. Kinetics of microtubule assembly were similar in preparations isolated from cerebral hemispheres of control and hyperthermic animals however, microtubules from the latter were altered in appearance and exhibited a higher degree of crosslinking.