Late Recruitment of Synapsin to Nascent Synapses Is Regulated by Cdk5

• Published in: Cell reports (Cambridge) Vol. 3; no. 4; pp. 1199 - 1212
• Main Authors: Easley-Neal, Courtney, Fierro, Javier, Buchanan, JoAnn, Washbourne, Philip
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.04.2013; Elsevier
• Subjects: Animals; Axons - metabolism; Cadherins - metabolism; Cyclin-Dependent Kinase 5 - metabolism; Danio rerio; Freshwater; Guanylate Kinases - metabolism; Synapses - metabolism; Synapses - ultrastructure; Synapsins - metabolism; Synaptic Vesicles - metabolism; Transport Vesicles - metabolism; Zebrafish
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2013.03.031

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. [Display omitted] •Synapsin is transported as a discrete packet•Recruitment of presynaptic components occurs in sequence•STVs precede PTVs, followed by synapsin transport packets•Synaptic stabilization of synapsin is regulated by Cdk5, not neuronal activity As the nervous system develops, synapses form through the transportation and targeting of discrete transport packets to neuron-neuron contact sites. By imaging the process of presynaptic assembly in living zebrafish embryos, Washbourne and colleagues identify a synapsin-containing transport particle, which is immobilized at synapses as part of a defined series of recruitment events. They show that local activation of cyclin-dependent kinase 5 (Cdk5) is necessary for this transport particle to be targeted to synapses. These studies reveal an underlying sequence to synaptogenesis.