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.
Thompson
K M
KM
Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec, Canada H3A 2B4.
Uetani
N
N
Manitt
C
C
Elchebly
M
M
Tremblay
M L
ML
Kennedy
T E
TE
D000818:Animals; D000911:Antibodies, Monoclonal; D001665:Binding Sites / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002490:Central Nervous System / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D005154:Facial Nerve / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D020439:Growth Cones / Q000201:enzymology* / Q000648:ultrastructure; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009416:Nerve Regeneration / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency* / Q000235:genetics; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2
D000911:Antibodies, Monoclonal; D006133:Growth Substances; D017027:Protein Tyrosine Phosphatases; C516885:Ptprs protein, mouse; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2