Kinesin-3 mediated delivery of presynaptic neurexin stabilizes growing dendritic spines and postsynaptic components in vivo

A high degree of cell and circuit-specific regulation has complicated efforts to precisely define roles for synaptic adhesion proteins in establishing circuit connectivity. Here, we take advantage of the strengths of C. elegans for cell-specific analyses to investigate molecular coordination of preand postsynaptic development. We show that developing dendritic spines emerge from the dendrites of wild type GABAergic motor neurons following the localization of active zone proteins and the formation of immature synaptic vesicle assemblies in presynaptic terminals. Similarly, clusters of postsynaptic receptors and F-actin are visible in GABAergic dendrites prior to spine outgrowth. Surprisingly, these developmental processes occur without a requirement for synaptic activity. Likewise, the initial stages of spine outgrowth and receptor clustering are not altered by deletion of the C. elegans ortholog of the transsynaptic adhesion protein, neurexin/NRX-1. Over time, however, dendritic spines and postsynaptic receptor clusters are destabilized in the absence of presynaptic NRX-1/neurexin and collapse prior to adulthood. The kinesin-3 family member, UNC-104, delivers NRX-1 to presynaptic terminals and ongoing UNC104 delivery is required into adulthood for the maintenance of postsynaptic structure. Our findings provide novel insights into the temporal order of synapse formation events in vivo and demonstrate a requirement for transsynaptic adhesion in stabilizing mature circuit connectivity. was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which this version posted May 11, 2021. ; https://doi.org/10.1101/2021.05.11.443328 doi: bioRxiv preprint