Sad-1 Background Information When a synapse is formed in C. elegans, presynaptic axon outgrowth is terminated, presynaptic clusters of vesicles are associated with active zone proteins and active zones are aligned with postsynaptic neurotransmitter receptors. A novel serine/threonine kinase, Sad-1, regulates several aspects of presynaptic differentiation. The Sad-1 mutant affects the presynaptic development of motor neurons as well as ASI neurons (1), which are a bilaterally symmetric pair of thermosensory neurons that control entry into the dauer larva stage (2). Sad-1, a 914 amino acid protein, is expressed in the nervous system and localizes to synapse-rich regions of the axons. Sad-1 is related to PAR-1, a kinase that regulates cell polarity during asymmetric cell division. Overexpression of Sad-1 causes mislocalization of vesicle proteins to dendrites, suggesting that Sad-1 plays a role in axonal-dentritic polarity and synaptic development (1). In sad-1 mutants, presynaptic vesicle clusters in sensory neurons and motor neurons are diffuse and disorganized. The sensory axons also fail to terminate in Sad-1 mutants, whereas Sad-1 overexpression causes sensory axons to terminate prematurely (3-5).
