The neuronal synapse is an asymmetric structure consisting of pre-synaptic and post-synaptic cell terminals in direct apposition to each other. This structure functions to mediate the transmission of signals between neurons and their targets. The formation of synapses is a tightly regulated process requiring the interaction of many genes and pathways. We are interested in identifying the genes that are required for controlling the proper formation of synapses. We have recently identified a protein complex that is involved in the control of synapse size and spacing. This SCF like ubiquitin ligase complex consists of the F-box protein FSN-1, the RING finger and GEF domain protein RPM-1, Skp1, and Cullin. We have shown that this complex is required pre-synaptically and is localized to a region surrounding the synapse called the peri-active zone. We hypothesize that this protein complex fine tunes and controls synapse formation by down regulating synapse promoting factors through an ubiquitin mediated process. In support of this theory we have identified a possible target or downstream effector of synapse formation in the receptor protein tyrosine kinase
scd-2 (suppressor of constitutive dauer). We have observed that protein levels of an SCD-2::GFP fusion protein increase in the absence of
fsn-1 in vivo. Preliminary results with an SCD-2 antibody show that endogenous levels of protein are increased in an
fsn-1 background. SCD-2 is predicted to be ubiquitinated by FSN-1 in our model and this is currently being tested. We have shown that loss of
scd-2 will partially rescue the synapse defects of
fsn-1 and
rpm-1. FSN-1 binds to the C-terminal kinase domain of SCD-2 in vitro. Suppression of
fsn-1 defects is specific for alleles of
scd-2 that are defective in the C-terminal kinase. The incomplete suppression of
fsn-1 by
scd-2 hints at the existence of other pathways or factors regulated by
fsn-1 and
rpm-1.