Synaptotagmin I Stabilizes Synaptic Vesicles via Its C2A Polylysine Motif

The synaptic vesicle protein, synaptotagmin 1, is a multifunctional protein required for several steps in the synaptic vesicle cycle. It is primarily composed of two calcium-binding domains, C(2)A and C2B. Within each of these domains, a polylysine motif has been identified that is proposed to mediate specific functions within the synaptic vesicle cycle. While the C2B polylysine motif plays an important role in synaptic transmission in vivo, the C(2)A polylysine motif has not previously been analyzed at an intact synapse. Here, we show that mutation of the C(2)A polylysine motif increases the frequency of spontaneous transmitter release in vivo. The increased frequency is not a developmental consequence of disrupted synaptic transmission, as evoked transmitter release is unimpaired in the mutants. Our results demonstrate that synaptotagmin I plays a direct role in regulating spontaneous transmitter release, indicative of an active role in synaptic vesicle stabilization mediated by the C(2)A polylysine motif. genesis 47:337-345, 2009. (C) 2009 Wiley-Liss, Inc.