Methylmercury-induced microtubule depolymerization leads to inhibition of tubulin synthesis

Methylmercury (MeHg) specifically depolymerizes microtubules and inhibits cell proliferation in mouse glioma cells. The effect of microtubule depolymerization by MeHg on tubulin synthesis was studied. Tubulin synthesis analyzed by two-dimensional electrophoresis using [35S]methionine as a tracer was markedly inhibited in mouse glioma cells exposed to 5 x 10(-6)M MeHg for 3 hr, which completely depolymerized microtubules. Under this condition, density of the protein bands other than tubulin in autoradiogram remained unchanged on gradient urea-polyacrylamide gels. Furthermore, the decrease in tubulin mRNA level was relevant to that in tubulin synthesis, although actin mRNA levels remained unchanged. In addition, specific transcription rates of beta-tubulin genes appeared to be unaffected under the same experimental condition as above. Thus, it is concluded that the disruption of microtubules by MeHg resulted in the inhibition of the synthesis of tubulin itself through autoregulatory repression in post-transcriptional processes as in the case of colchicine treatment.