Synaptotagmin-1 and -7 Are Redundantly Essential for Maintaining the Capacity of the Readily-Releasable Pool of Synaptic Vesicles

In forebrain neurons,ca2+ triggers exocytosis of readily releasable vesicles by binding to synaptotagmin-1 and -7,thereby inducing fast and slow vesicle exocytosis,respectively. loss-of-function of synaptotagmin-1 or -7 selectively impairs the fast and slow phase of release,respectively,but does not change the size of the readily-releasable pool (rrp) of vesicles as measured by stimulation of release with hypertonic sucrose,or alter the rate of vesicle priming into the rrp. here we show,however,that simultaneous loss-of-function of both synaptotagmin-1 and -7 dramatically decreased the capacity of the rrp,again without altering the rate of vesicle priming into the rrp. either synaptotagmin-1 or -7 was sufficient to rescue the rrp size in neurons lacking both synaptotagmin-1 and -7. although maintenance of rrp size was ca2+-independent,mutations in ca2+-binding sequences of synaptotagmin-1 or synaptotagmin-7—which are contained in flexible top-loop sequences of their c2 domains—blocked the ability of these synaptotagmins to maintain the rrp size. both synaptotagmins bound to snare complexes; snare complex binding was reduced by the top-loop mutations that impaired rrp maintenance. thus,synaptotagmin-1 and -7 perform redundant functions in maintaining the capacity of the rrp in addition to nonredundant functions in the ca2+ triggering of different phases of release. © 2015 bacaj et al.