This end-accumulation phenotype of GFP::RAB-3 in dhc-1 mutants is inhibited in dhc-1; cdk-5, but not in dhc-1; cyy-1, double mutants ( Figure 8F), indicating that CDK-5, but not CYY-1, contributes to the end accumulation of GFP::RAB-3. These data further support R428 price that CDK-5 and UNC-104 act together in the process of new dorsal synapse formation during DD remodeling. Taken together, we propose that two different microtubule motors interplay temporally for proper localization of new synapses during the remodeling process ( Figure 8G). In the present study, our data showed
that destruction of existing synapse is regulated by a cyclin box-containing protein CYY-1. The disassembled synaptic components are then transported to the dorsal processes of DDs by an axonal transport motor UNC-104/Kinesin3. In the absence of CDK-5, dorsal synapse formation during remodeling is significantly delayed, possibly also due to insufficient activation of UNC-104/Kinesin3-mediated axonal transport. Once CDK-5 and UNC-104/Kinesin3 Obeticholic Acid supplier bring the synaptic components to the dorsal axon through the commissure, the synaptic components are finally
positioned at the proper synaptic locations by dynein complexes (Figure S7). The stereotyped reversal of synaptic connectivity of DD motoneurons during C. elegans development has long been considered as an attractive model system to study synaptic plasticity ( White et al., 1978 and Hallam and Jin, 1998). While it has been well established that the ventral synapses in the L1 animal are eventually eliminated, and the new synapses are formed in the dorsal axon, the relationship between synapse formation and elimination has not been well understood. By specifically labeling the presynaptic
terminals of the DD neurons and performing time course experiments, we have been able to directly visualize the remodeling process in vivo. Interestingly, we found that the elimination of existing synapses and the formation of new synapses occur simultaneously within a certain time window during the DD remodeling Dipeptidyl peptidase process ( Figure S1). This is analogous to many observations made in the vertebrate systems. For example, retinal ganglion axons form synapses with tectal neurons through a dynamic process characterized by concurrent synapse formation and elimination in the same presynaptic axon ( Debski and Cline, 2002 and Ruthazer et al., 2006). In the well-studied vertebrate neuromuscular junction, an initial stage of synapse formation leads to each muscle fiber being innervated by multiple motor axons, which is then followed by a period of synaptic competition, resulting in the mature monoinnervation pattern. During the activity-driven competition, one of the motor axons gains its innervation, while other axons lose their synaptic connections to each particular muscle fiber, suggesting that synapse formation and elimination take place concurrently in the same postsynaptic muscle ( Lichtman and Colman, 2000).