The Two Isoforms of the<i>Caenorhabditis elegans</i>Leukocyte-Common Antigen Related Receptor Tyrosine Phosphatase PTP-3 Function Independently in Axon Guidance and Synapse Formation

TLDR

LAR‑like phosphatase receptors are conserved cell‑adhesion molecules involved in multiple developmental processes, and in C. elegans the ptp‑3 gene encodes two isoforms that differ in their extracellular domains. The study proposes that PTP‑3A functions as a molecular link between the extracellular matrix and the intracellular adaptor α‑liprin during synaptogenesis. PTP‑3A is hypothesized to connect the ECM component nidogen to α‑liprin, thereby mediating synapse formation.

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 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.