The SAD-1 kinase regulates presynaptic vesicle clustering and axon termination

During synapse formation, presynaptic axon outgrowth is terminated, presyna ptic clusters of vesicles are associated with active zone proteins, and act ive zones are aligned with postsynaptic neurotransmitter receptors. We repo rt here the identification of a novel serine/threonine kinase, SAD-1,that r egulates several aspects of presynaptic differentiation in C. elegans. In s ad-1 mutant animals presynaptic vesicle clusters in sensory neurons and mot or neurons are diffuse and disorganized. Sensory axons fail to terminate in sad-1 mutants, whereas overexpression of SAD-1 causes sensory axons to ter minate prematurely. SAD-1 protein is expressed in the nervous system and lo calizes to synapse-rich regions of the axons. SAD-1 is related to PAR-1, a kinase that regulates cell polarity during asymmetric cell division. Overex pression of SAD-1 causes mislocalization of vesicle proteins to dendrites, suggesting that sad-1 affects axonal-dendritic polarity as well as synaptic development.