THE ROLES OF CALMODULIN, ACTIN, AND VIMENTIN IN STEROID-SYNTHESIS BY ADRENAL-CELLS

The rate of steroid synthesis is regulated by the I ate of transport o f cholesterol to mitochondria. The transport process involves Two elem ents of the cytoskeleton (microfilaments and intermediate filaments) a nd Ca2+/ calmodulin. Electron microscopy and immunofluorescence reveal that lipid droplets in which steroidogenic cholesterol is stored in t he cytoplasm are tightly attached to vimentin intermediate filaments. Mitochondria are also attached to intermediate filaments. Ca2+/calmadu lin is known to be essential for the steroidogenic response to ACTH an d acts to increase transport of cholesterol to mitochondria. Ca2+/calm odulin promotes phosphorylation of two important adrenal proteins: vim entin via its protein kinase and myosin light chain via the calmodulin -dependent light-chain kinase. In permeabilized adrenal cells Ca2+/cal modulin causes an ATP-dependent contraction of the cells. Phosphorylat ion of vimentin is known to cause breakdown of intermediate filaments. Electron microscopy reveals that actin filaments cross-link intermedi ate filaments in adrenal cells. It is proposed that ACTH has at least two second messengers, Ca2+/calmodulin and cAMP. Ca2+/calmodulin cause s breakdown of vimentin filaments and activates a contractile event de pendent on ATP and myosin light chain. These changes reorganize the cy toskeleton in such a way as to facilitate the interaction of lipid dro plets with mitochondria, resulting in transport of cholesterol to thes e organelles and hence increased steroid synthesis. (C) 1997 by Elsevi er Science Inc.