Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Genetically Modified
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Axons / metabolism
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Caenorhabditis elegans / cytology*
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / growth & development
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Caenorhabditis elegans / metabolism*
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Cell Polarity
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Dendrites / metabolism
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Gene Expression Regulation, Developmental
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Genes, Helminth
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Intracellular Signaling Peptides and Proteins
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Microfilament Proteins / genetics
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Microfilament Proteins / metabolism*
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Motor Neurons / cytology
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Motor Neurons / metabolism
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Mutation
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Neurons / cytology*
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Neurons / metabolism*
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Neurons, Afferent / cytology
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Neurons, Afferent / metabolism
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Phosphorylation
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Presynaptic Terminals / metabolism
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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RNA Interference
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Synapses / metabolism
Substances
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Caenorhabditis elegans Proteins
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Intracellular Signaling Peptides and Proteins
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Microfilament Proteins
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Nerve Tissue Proteins
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Protein Isoforms
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neurabin
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sad-1 protein, C elegans
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Protein Serine-Threonine Kinases