Receptor protein tyrosine phosphatase sigma inhibits axonal regeneration and the rate of axon extension.

Transgenic mice lacking receptor protein tyrosine phophatase-sigma (RPTPsigma), a type IIa receptor protein tyrosine phosphatase, exhibit severe neural developmental deficits. Continued expression of RPTPsigma in the adult suggests that it plays a functional role in the mature nervous system. To determine if RPTPsigma might influence axonal regeneration, the time course of regeneration following facial nerve crush in wild-type and RPTPsigma (-/-) mice was compared. Mice lacking RPTPsigma exhibited an accelerated rate of functional recovery. Immunocytochemical examination of wild-type neurons in cell culture showed RPTPsigma protein in the growth cone. To determine if RPTPsigma affects the ability of a neuron to extend an axon, the rate of axon growth in neuronal cultures derived from wild-type and RPTPsigma (-/-) embryonic mice was compared. RPTPsigma did not affect the rate of axon initiation, but the rate of axon extension is enhanced in neurons obtained from RPTPsigma (-/-) mice. These findings indicate that RPTPsigma slows axon growth via a mechanism intrinsic to the neuron and identify a role for RPTPsigma regulating axonal regeneration by motoneurons.