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Development ePress online publication date 6 Dec 2006
doi: 10.1242/dev.02725

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Research article

Neuronal polarity is regulated by a direct interaction between a scaffolding protein, Neurabin, and a presynaptic SAD-1 kinase in Caenorhabditis elegans


Wesley Hung, Christine Hwang, Michelle D. Po, and Mei Zhen*
* Author for correspondence (e-mail: zhen{at}mshri.on.ca)

The establishment of axon-dendrite identity in developing neurites is essential for the development of a functional nervous system. The SAD serine-threonine kinases have been implicated in regulating neuronal polarization and synapse formation. Here, we show that the C. elegans SAD-1 kinase regulates axonal identity and synapse formation through distinct mechanisms. We identified a scaffolding protein, Neurabin (NAB-1), as a physiological binding partner of SAD-1. Both sad-1 and nab-1 loss-of-function mutants display polarity defects in which synaptic vesicles accumulate in both axons and dendrites. We show that sad-1 and nab-1 function in the same genetic pathway to restrict axonal fate. Unlike sad-1, nab-1 mutants display normal morphology of vesicle clusters. Strikingly, although the physical interaction of NAB-1 with SAD-1 is necessary for polarity, it is dispensable for synapse morphology. We propose that Neurabin functions as a scaffold to facilitate SAD-1-mediated phosphorylation for substrates specific for restricting axonal fate during neuronal polarization.


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