ANNEXIN VI BINDS TO A SYNAPTIC VESICLE PROTEIN, SYNAPSIN-I

Annexin VI bound to > 14 species of proteins in the whole homogenate of rat forebrain in a Ca2+/phosphatidylserine- or phosphatidic acid-dependent manner. When the subcellular fractions of rat forebrain were examined with a blot from a sodium dodecyl sulfate-polyacrylamide gel, each annexin VI-binding protein showed a different distribution, suggesting that annexin VI is a multifunctional protein. Of these proteins, the doublers of M(r) 80,000 were enriched in the purified synaptic vesicles and were identified as synapsin I. Annexin VI bound to the head domain of synapsin I. When the binding of annexin VI to synapsin I was characterized in the native state, the affinity of the binding for Ca2+ (K-Ca) was 12.6 mu M and the affinity for annexin VI (K-D) was similar to 270 nM. Phosphorylation of synapsin I by cyclic AMP-dependent protein kinase and by Ca2+/calmodulin-dependent protein kinase II inhibited the annexin VI binding. The mode of the inhibition was different between the two kinases. These results indicate that annexin VI may modulate the function of synapsin I in a Ca2+- and phospholipid-dependent manner.