How synapsin I may cluster synaptic vesicles

Synapsin I is the most abundant brain phosphoprotein present in conventional synapses of the CNS. Knockout and rescue experiments have demonstrated that synapsin is essential for clustering of synaptic vesicles (SVs) at active zones and the organization of the reserve pool of SVs. However, in spite of intense efforts it remains largely unknown how exactly synapsin I performs this function. It has been proposed that synapsin I in its dephosphorylated state may tether SVs to actin filaments within the cluster from where SVs are released in response to activity-induced synapsin phosphorylation. Recent studies, however, have failed to detect actin filaments inside the vesicle cluster at resting central synapses. Instead, proteins with established functional roles in SV recycling have been found within this presynaptic compartment. Here we discuss potential alternative mechanisms of synapsin I-dependent SV clustering in the reserve pool.

► In this review we examine potential mechanisms involved in organization of synaptic vesicles in the reserve pool in central synapses.
► We show that in addition to synapsin I a number of proteins with established roles in endocytosis are localized in the synaptic vesicle pool at rest.
► We point out that the endocytic proteins localized in the reserve pool of synaptic vesicles may interact with each other and with synapsin I.
► We propose that endocytic molecules together with synapsins form an intervesicular matrix, which organizes vesicles in the reserve pool of synaptic vesicles.