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

Abstract

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