Altered MAP kinase phosphorylation and impaired motor coordination in PTPRR deficient mice.
The neuronal protein tyrosine phosphatases encoded by mouse gene Ptprr (PTPBR7, PTP-SL, PTPPBSgamma-42 and PTPPBSgamma-37) have been implicated in mitogen-activated protein (MAP) kinase deactivation on the basis of transfection experiments. To determine their physiological role in vivo, we generated mice that lack all PTPRR isoforms. Ptprr-/- mice were viable and fertile, and not different from wildtype littermates regarding general physiology or explorative behaviour. Highest PTPRR protein levels are in cerebellum Purkinje cells, but no overt effects of PTPRR deficiency on brain morphology, Purkinje cell number or dendritic branching were detected. However, MAP kinase phosphorylation levels were significantly altered in the PTPRR-deficient cerebellum and cerebrum homogenates. Most notably, increased phospho-ERK1/2 immunostaining density was observed in the basal portion and axon hillock of Ptprr-/- Purkinje cells. Concomitantly, Ptprr-/- mice displayed ataxia characterized by defects in fine motor coordination and balance skills. Collectively, these results establish the PTPRR proteins as physiological regulators of MAP kinase signalling cascades in neuronal tissue and demonstrate their involvement in cerebellum motor function.
Chirivi
Renato G S
RG
Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Noordman
Yvet E
YE
Van der Zee
Catharina E E M
CE
Hendriks
Wiljan J A J
WJ
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000473:pathology; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019957:Motor Skills Disorders / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency*; D054634:Receptor-Like Protein Tyrosine Phosphatases, Class 7
D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases; D017027:Protein Tyrosine Phosphatases; C513472:Ptprr protein, mouse; D054634:Receptor-Like Protein Tyrosine Phosphatases, Class 7