Reference - Detail
|Author||Ackley BD, Harrington RJ, Hudson ML, Williams L, Kenyon CJ, Chisholm AD, Jin Y.|
|Title||The two isoforms of the Caenorhabditis elegans leukocyte-common antigen related receptor tyrosine phosphatase PTP-3 function independently in axon guidance and synapse formation.|
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.
|MeSH||Animals Animals, Genetically Modified Axons / metabolism* Axons / physiology Caenorhabditis elegans / enzymology* Caenorhabditis elegans Proteins / biosynthesis Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* Intracellular Signaling Peptides and Proteins / genetics Mutation Nerve Tissue Proteins / biosynthesis* Nerve Tissue Proteins / genetics Protein Isoforms / biosynthesis Protein Isoforms / genetics Protein Isoforms / physiology Protein Tyrosine Phosphatase, Non-Receptor Type 11 Protein Tyrosine Phosphatases / biosynthesis* Protein Tyrosine Phosphatases / genetics Receptor-Like Protein Tyrosine Phosphatases, Class 2 Receptors, Cell Surface / biosynthesis* Receptors, Cell Surface / genetics Synapses / genetics Synapses / metabolism*|