Ca(2+)-dependent phosphorylation of synapsin I as a possible regulatory mechanism of neurosecretion

Phosphorylation of homogeneous synapsin I isolated from human brain by Ca2+, phospholipid-dependent protein kinase (protein kinase C) from the same source was studied. The inhibitory effect of calmodulin on this process was demonstrated. The kinetics of activation of synapsin I phosphorylation by acidic phospholipids, phosphatidylserine and phosphatidylinositol, in the absence and presence of phosphatidylinositol-4,5-bisphosphate and diacylglycerol was compared. The proteolytic effect of degradation of the synapsin I molecule phosphorylated by Ca2+, calmodulin-dependent protein kinase II was revealed. No proteolysis of synapsin phosphorylated under similar conditions either by protein kinase C or cAMP-dependent protein kinase was detected. In view of the process specificity, the physiological significance of the observed effect is suggested. The inter-relationship between two ways of neurosecretion regulation is discussed: an earlier known, conventional way, mediated by synapsin I phosphorylation by Ca2+, calmodulin-dependent protein kinase II, and another one, mediated by synapsin I phosphorylation by protein kinase C. The modulating role of polyphosphoinositides in the PK C-dependent way of regulation is considered.