The roles of calmodulin, actin, and vimentin in steroid synthesis by adrenal cells.
The rate of steroid synthesis is regulated by the rate of transport of cholesterol to mitochondria. The transport process involves two elements of the cytoskeleton (microfilaments and intermediate filaments) and Ca2+/ calmodulin. Electron microscopy and immunofluorescence reveal that lipid droplets in which steroidogenic cholesterol is stored in the cytoplasm are tightly attached to vimentin intermediate filaments. Mitochondria are also attached to intermediate filaments. Ca2+/calmodulin is known to be essential for the steroidogenic response to ACTH and acts to increase transport of cholesterol to mitochondria. Ca2+/ calmodulin promotes phosphorylation of two important adrenal proteins: vimentin via its protein kinase and myosin light chain via the calmodulin-dependent light-chain kinase. In permeabilized adrenal cells Ca2+/calmodulin causes an ATP-dependent contraction of the cells. Phosphorylation of vimentin is known to cause breakdown of intermediate filaments. Electron microscopy reveals that actin filaments cross-link intermediate filaments in adrenal cells. It is proposed that ACTH has at least two second messengers, Ca2+/calmodulin and cAMP. Ca2+/calmodulin causes breakdown of vimentin filaments and activates a contractile event dependent on ATP and myosin light chain. These changes reorganize the cytoskeleton in such a way as to facilitate the interaction of lipid droplets with mitochondria, resulting in transport of cholesterol to these organelles and hence increased steroid synthesis.
Hall
P F
PF
Department of Endocrinology, Prince of Wales Hospital, Sydney, Australia.
D000199:Actins / Q000378:metabolism*; D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008928:Mitochondria / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D014746:Vimentin / Q000378:metabolism*
D000199:Actins; D002147:Calmodulin; D008055:Lipids; D013256:Steroids; D014746:Vimentin; D002118:Calcium