Abstract
Leukocyte-common antigen related (LAR)-like phosphatase receptors are conserved cell adhesion molecules that function in multiple developmental processes. The Caenorhabditis elegans ptp-3 gene encodes two LAR family isoforms that differ in the extracellular domain. We show here that the long isoform, PTP-3A, localizes specifically at synapses and that the short isoform, PTP-3B, is extrasynaptic. Mutations in ptp-3 cause defects in axon guidance that can be rescued by PTP-3B but not by PTP-3A. Mutations that specifically affect ptp-3A do not affect axon guidance but instead cause alterations in synapse morphology. Genetic double-mutant analysis is consistent with ptp-3A acting with the extracellular matrix component nidogen, nid-1, and the intracellular adaptor alpha-liprin, syd-2. nid-1 and syd-2 are required for the recruitment and stability of PTP-3A at synapses, and mutations in ptp-3 or nid-1 result in aberrant localization of SYD-2. Overexpression of PTP-3A is able to bypass the requirement for nid-1 for the localization of SYD-2 and RIM. We propose that PTP-3A acts as a molecular link between the extracellular matrix and alpha-liprin during synaptogenesis.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Genetically Modified
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Axons / metabolism*
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Axons / physiology
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Caenorhabditis elegans / enzymology*
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Caenorhabditis elegans Proteins / biosynthesis
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / physiology*
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Intracellular Signaling Peptides and Proteins / genetics
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Mutation
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Nerve Tissue Proteins / biosynthesis*
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Nerve Tissue Proteins / genetics
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Protein Isoforms / biosynthesis
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Protein Isoforms / genetics
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Protein Isoforms / physiology
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatases / biosynthesis*
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Protein Tyrosine Phosphatases / genetics
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Receptor-Like Protein Tyrosine Phosphatases, Class 2
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Receptors, Cell Surface / biosynthesis*
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Receptors, Cell Surface / genetics
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Synapses / genetics
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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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Nerve Tissue Proteins
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Protein Isoforms
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Receptors, Cell Surface
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatases
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Receptor-Like Protein Tyrosine Phosphatases, Class 2