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-domain as the largest conserved domain. The C-domain is structurally homologous to ATPases, suggesting that synapsins function as ATP-dependent phosphotransfer enzymes. We have now identified an unanticipated third synapsin gene that is also expressed in brain. The product of this gene, synapsin IIIa, shares with synapsins Ia and IIa three conserved domains that are connected by variable sequences: the phosphorylated A-domain at the amino terminus, the large ATP-binding C-domain in the center, and the E-domain at the carboxyl terminus. Like other synapsins, synapsin IIIa binds ATP with high affinity and ADP with a lower affinity, consistent with a cycle of ATP binding and hydrolysis. ATP binding to the different synapsins is directly regulated by Ca2+ in a dramatically different fashion: Ca2+ activates ATP binding to synapsin I, has no effect on synapsin II, and inhibits synapsin III. Thus vertebrates express three distinct synapsins that utilize ATP but are specialized for different modes of direct Ca2+ regulation in synaptic function.
Hosaka
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Center for Basic Neuroscience, Department of Molecular Genetics, and Howard Hughes Medical Institute, The University of Texas Southwestern Medical School, Dallas, Texas 75235, USA.
Südhof
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TC
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D016704:Synapsins
D009479:Neuropeptides; D010750:Phosphoproteins; D011994:Recombinant Proteins; C111812:SYN3 protein, human; D016704:Synapsins; D000255:Adenosine Triphosphate; D002118:Calcium