THE COOH TERMINUS OF SYNAPTOTAGMIN MEDIATES INTERACTION WITH THE NEUREXINS

The interaction of the synaptic vesicle protein, synaptotagmin, and th e presynaptic alpha-latrotoxin receptor, a neurexin, has been proposed to be involved in docking of synaptic vesicles at active sites or mod ulation of neurotransmitter release. Here I report the investigation o f the domain of synaptotagmin responsible for this interaction. Pieces of synaptotagmin containing the carboxyl terminus are capable of puri fying neurexins from solubilized brain homogenates. Pieces as small as a synthesized peptide corresponding to the COOH-terminal 34 amino aci ds are capable of enriching neurexins 100-fold. The binding of neurexi ns to synaptotagmin is calcium-independent and of moderate affinity. T his COOH-terminal segment of synaptotagmin is conserved in all species characterized to date. Reflective of this, a synthetic peptide corres ponding to the carboxyl terminus of Drosophila synaptotagmin is capabl e of purification of rat neurexins, suggesting the possibility that th is interaction may also exist in Drosophila. I propose that the carbox yl terminus of synaptotagmin binds to the carboxyl terminus of the neu rexins and that this interaction may mediate docking of synaptic vesic les or modulation of neurotransmitter release.