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LAR-Like Receptor Tyrosine Kinases in C. elegans

Receptor protein tyrosine phosphatases include the leukocyte-common antigen related (LAR) family of cell adhesion molecules. In Caenorhabditis elegans, the LAR-like gene ptp-3 encodes two distinct isoforms, PTP-3A and PTP-3B. Compared with PTP-3A, the extracellular domain of PTP-3B lacks the Ig-like domain and the first four fibronectin type III repeats, but their intracellular domains are identical. This week, Ackley et al. delineate independent roles for these isoforms in axon guidance and synapse formation. They created isoform-specific green fluorescent protein fusion transgenes to determine expression patterns. Whereas PTP-3A overlapped with UNC-10 and SYD-2 at presynaptic sites, PTP-3B was expressed extrasynaptically in a temporally regulated pattern. The PTP-3 mutations mu256 and op147 exhibited axon projection defects that were rescued only by expression of PTP-3B. In contrast, synaptic defects in the mutants were rescued by PTP-3A expression. From genetic doublemutant analysis, the authors surmised that PTP-3A links the extracellular matrix protein nidogen and the intracellular adaptor -liprin, perhaps stabilizing synapses.