The Two Isoforms of theCaenorhabditis elegansLeukocyte-Common Antigen Related Receptor Tyrosine Phosphatase PTP-3 Function Independently in Axon Guidance and Synapse Formation

Abstract

Leukocyte-common antigen related (LAR)-like phosphatase receptors are conserved cell adhesion molecules that function in multiple developmental processes. TheCaenorhabditis elegans ptp-3gene 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 inptp-3cause defects in axon guidance that can be rescued by PTP-3B but not by PTP-3A. Mutations that specifically affectptp-3Ado not affect axon guidance but instead cause alterations in synapse morphology. Genetic double-mutant analysis is consistent withptp-3Aacting with the extracellular matrix component nidogen,nid-1, and the intracellular adaptor α-liprin,syd-2.nid-1andsyd-2are required for the recruitment and stability of PTP-3A at synapses, and mutations inptp-3ornid-1result in aberrant localization of SYD-2. Overexpression of PTP-3A is able to bypass the requirement fornid-1for 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.