Neuronal polarity is regulated by a direct interaction between a scaffolding protein, Neurabin, and a presynaptic SAD-1 kinase in Caenorhabditis elegans.
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.
Hung
Wesley
W
Samuel Lunenfeld Research Institute, Mount Sinai Hospital and Department of Microbiology and Medical Genetics, University of Toronto, Ontario, M5G 1X5, Canada.
Hwang
Christine
C
Po
Michelle D
MD
Zhen
Mei
M
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity; D003712:Dendrites / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D017729:Presynaptic Terminals / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D013569:Synapses / Q000378:metabolism; D000099273:Neurabins
D029742:Caenorhabditis elegans Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases; D000099273:Neurabins; C421165:sad-1 protein, C elegans