Late Recruitment of Synapsin to Nascent Synapses Is Regulated by Cdk5

Synapse formation is a complex process that involves the recruitment and assembly of a myriad of pre- and postsynaptic proteins. Despite being present at every synapse in the vertebrate CNS, little is known about the transport, recruitment, and stabilization of synapsin at nascent synapses during development. We examined the transport and recruitment of synapsin to nascent presynaptic terminals in vivo in the developing zebrafish spinal cord. Synapsin was transported in a transport packet independently of two other presynaptic organelles: synaptic vesicle (SV) protein transport vesicles (STVs) and Piccolo-containing active zone precursor transport vesicles (PTVs). During presynaptic assembly, recruitment of all three transport packets occurred in an ordered sequence: STVs preceded PTVs, which in turn preceded synapsin. Importantly, cyclin-dependent kinase 5 (Cdk5) specifically regulated the late recruitment of synapsin transport packets at synapses. These results point to additional layers of complexity in the established mechanisms of synaptogenesis.