PT - JOURNAL ARTICLE AU - Brian D. Ackley AU - Robert J. Harrington AU - Martin L. Hudson AU - Lisa Williams AU - Cynthia J. Kenyon AU - Andrew D. Chisholm AU - Yishi Jin TI - The Two Isoforms of the <em>Caenorhabditis elegans</em> Leukocyte-Common Antigen Related Receptor Tyrosine Phosphatase PTP-3 Function Independently in Axon Guidance and Synapse Formation AID - 10.1523/JNEUROSCI.2010-05.2005 DP - 2005 Aug 17 TA - The Journal of Neuroscience PG - 7517--7528 VI - 25 IP - 33 4099 - http://www.jneurosci.org/content/25/33/7517.short 4100 - http://www.jneurosci.org/content/25/33/7517.full SO - J. Neurosci.2005 Aug 17; 25 AB - 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 α-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 α-liprin during synaptogenesis.