Formation of synapses is essential for establishing neural circuits during the development of a nervous system. Signaling mechanisms that control the initiation and maintenance of synapses, however, remain largely unknown. SAD-1 family serine/threonine kinase was first identified in C. elegans in genetic screens designed to isolate mutations affecting synaptogenesis. Loss of
sad-1 functions results in a variable and wide range of synaptic development defects including diffuse distribution of synaptic vesicles at some synapses, failure to develop synapses in certain axonal regions, and axons passing their targets. These observations strongly suggest that SAD-1 kinase activity is a key factor to promote the formation of synapses (Crump et al., Neuron. 2001 1:115-29). The presence of fly, mouse and human homologues as revealed by BLAST search suggests that SAD-1 function is evolutionarily conserved. Further elucidating the SAD-1 signaling pathways would thus provide insights on mechanisms regulating synaptogenesis. In a yeast two-hybrid screen, we have identified several potential interacting proteins of SAD-1. Out of the screen, we identified a homologue of mammalian neurabin gene,
nab-1. Like the mammalian homologue, NAB-1 is expressed in the nervous system. Preliminary results suggest that NAB-1 interacts with SAD-1 through its PDZ domain. In addition, two novel genes were identified to interact with SAD-1.
sai-1, SAD-1 interacting protein, encodes a novel zinc finger containing protein that expresses solely in the nervous system and shows co-localization with SAD-1. Many proteins involved in synapse function, such as Picolo and Rim1/unc-10, have been shown to interact with other proteins through their zinc finger domains.
sai-2 encodes a novel protein with homology to S. cerevisiae Vps36, which is involved in vacuolar protein sorting. Expression studies of
sai-2 revealed that it is expressed in the nervous system as well as the muscle dense bodies. Further studies will be presented to elucidate the roles of these genes in synaptogenesis.