Identification of a cell adhesion molecule involved in negative regulation of presynaptic assembly in C.elegans

Abstract

Synapses are asymmetric structures that are specialized for neuronal signal transduction. The molecular mechanisms of how the assembly of presynaptic components is initiated and regulated remain unknown. In C. elegans hermaphrodite‐specific motor neurons HSN, SYD‐1 (a conserved protein with PDZ, C2 and RhoGAP domains) and SYD‐2 (a Liprin‐α adapter protein) are essential for the assembly of presynaptic components at synaptic region. Loss‐of‐function of syd‐1 or syd‐2 causes failure in the formation of presynaptic structure at normal synaptic location, which results in abnormal egg‐laying behavior. To further understand the molecular mechanisms, we carried out genetic suppressor screen of syd‐1. We identified a mutant that restored egg‐laying defects and partially improved the localization of synaptic vesicle markers at synaptic sites in HSN in syd‐1 loss‐of‐function animals. The mutant weakly suppressed egg‐laying defects and synaptic defects in HSN in syd‐2 loss‐of‐function. The responsible gene encodes a non‐classical cadherin protein. Future characterization of the mutant may contribute to our understanding of molecular mechanisms of presynaptic assembly.