An integrated approach to secretion. Phosphorylation and Ca2+-dependent binding of proteins associated with chromaffin granules.

Pharmacological and morphological studies of secretion from bovine chromaffin cells indicate that the nicotinic receptor initiates intracellular signaling. An increase in [Ca2+]i is a necessary but not sufficient element for secretion. Receptor-dependent, but intracellular-Ca2+-independent alterations of the organization of cortical zone allows close approach of chromaffin granules and plasma membrane. Chromaffin granules possess both Ca2+-dependent and Ca2+-independent protein kinases, but the major substrates for these kinases appear to be associated with other organelles or to be soluble cytosolic proteins. Quantitatively the most important Ca2+-dependent cytosolic components that interact with the chromaffin granule do not show strict specificity for this secretory organelle, but are widely distributed in different cell types and are localized at or close to the plasma membrane in intact chromaffin and other cells. These molecules are closely related in biochemical properties and sequence and include substrates for membrane-associated kinases. Two of these proteins (caldesmon and p36) have binding sites for F-actin; the others described have binding sites for acidic phospholipids.