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.
Ackley
Brian D
BD
Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Cruz, California 95064, USA.
Harrington
Robert J
RJ
Hudson
Martin L
ML
Williams
Lisa
L
Kenyon
Cynthia J
CJ
Chisholm
Andrew D
AD
Jin
Yishi
Y
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D017173:Caenorhabditis elegans / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2