SYNAPSIN-III, A NOVEL SYNAPSIN WITH AN UNUSUAL REGULATION BY CA2+

Synapsins I and II are synaptic vesicle proteins essential for normal Ca2+ regulation of neurotransmitter release. Synapsins are composed of combinations of common and variable sequences, with the central C-dom ain as the largest conserved domain. The C-domain is structurally homo logous to ATPases, suggesting that synapsins function as ATP-dependent phosphotransfer enzymes. We have now identified an unanticipated thir d synapsin gene that is also expressed in brain, The product of this g ene, synapsin IIIa, shares with synapsins Ia and IIa three conserved d omains that are connected by variable sequences: the phosphorylated A- domain at the amino terminus, the large ATP-binding C domain in the ce nter, and the E-domain at the carboxyl terminus, Like other synapsins, synapsin IIIa binds ATP with high affinity and ADP with a lower affin ity, consistent with a cycle of ATP binding and hydrolysis, ATP bindin g to the different synapsins is directly regulated by Ca2+ in a dramat ically different fashion: Ca2+ activates ATP binding to synapsin I, ha s no effect on synapsin II, and inhibits synapsin III. Thus vertebrate s express three distinct synapsins that utilize ATP but are specialize d for different modes of direct Ca2+ regulation in synaptic function.