Isoform-specific binding of the tyrosine phosphatase PTPsigma to a ligand in developing muscle

PTPsigma is a receptor tyrosine phosphatase that is expressed widely in the developing nervous system and that controls the growth and retinotopic mapping of retinal axons. PTPsigma is also expressed in motor neurons where its function is unclear. Given that invertebrate relatives of PTPsigma can control motor axon guidance, target contact, and synaptogenesis, we have asked if extracellular ligands exist for cPTPsigma, the avian PTPsigma orthologue, in the neuromuscular system. Of the two major isoforms cPTPsigma1 and cPTPsigma2, only the shorter cPTPsigma1 isoform is expressed in developing spinal motor neurons and their axons. We show that ectodomains of cPTPsigma1, but not of cPTPsigma2, bind specifically to developing skeletal myotubes. The putative myotube ligand is not related to the previously described binding of cPTPsigma to heparan sulfates within the proteoglycans agrin and collagen XVIII, since heparinase treatment of myotubes does not alter cPTPsigma1 binding and since most mutations that abolish binding of cPTPsigma1 to heparin do not affect myotube binding. The expression of cPTPsigma1 in motor axons and its direct binding to target myotubes suggest an isoform-specific role for axonally expressed cPTPsigma1 during establishment or maintenance of neuromuscular contacts.