Function and regulation of calmodulin in endocrine cells

Abstract

Calmodulin is the major intracellular receptor for Ca 2+ in all eukaryotic cells. This protein binds Ca 2+ with high affinity, has no alternative function, has multiple acceptor protein and is ubiquitous and structurally conserved. Calmodulin is constituatively expressed in 13 hormone-dependent systems. However the protein is elevated in both endocrine and non-endocrine tumors compared to non-transformed counterparts. The synthesis of Calmodulin is also regulated during the cell cycle and is restricted to the g 1/s boundary. Anti-calmodulin drugs can selectively and reversibly block cells in early S. The data are compatible with a role for Calmodulin in DNA synthesis. One of the major calmodulin acceptor proteins present in all cells is the myosin light chain kinase (MLCK). Both CaM and MLCK are localized on stress fibers in the cytoplasm of interphase cells and appear to be one primary enzyme system responsible for the Ca 2+-dependent regulation of secretion from endocrine cells. Calmodulin and MLCK are also found in the nucleoli of interphase cells by light and electron-microscopic as well as by biochemical techniques. These molecules are restricted to the fibrillar component of the nucleolus and the localization is markedly altered by actinomycin D. Calcium is known to regulate the structure of nucleoli by a mechanism involving contractility. Our data suggest that this mechanism may be dependent upon CaM and MLCK.