Receptor protein tyrosine phosphatase alpha is essential for hippocampal neuronal migration and long-term potentiation.
Despite clear indications of their importance in lower organisms, the contributions of protein tyrosine phosphatases (PTPs) to development or function of the mammalian nervous system have been poorly explored. In vitro studies have indicated that receptor protein tyrosine phosphatase alpha (RPTPalpha) regulates SRC family kinases, potassium channels and NMDA receptors. Here, we report that absence of RPTPalpha compromises correct positioning of pyramidal neurons during development of mouse hippocampus. Thus, RPTPalpha is a novel member of the functional class of genes that control radial neuronal migration. The migratory abnormality likely results from a radial glial dysfunction rather than from a neuron-autonomous defect. In spite of this aberrant development, basic synaptic transmission from the Schaffer collateral pathway to CA1 pyramidal neurons remains intact in Ptpra(-/-) mice. However, these synapses are unable to undergo long-term potentiation. Mice lacking RPTPalpha also underperform in the radial-arm water-maze test. These studies identify RPTPalpha as a key mediator of neuronal migration and synaptic plasticity.
Petrone
Angiola
A
Department of Pharmacology, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Battaglia
Fortunato
F
Wang
Cheng
C
Dusa
Adina
A
Su
Jing
J
Zagzag
David
D
Bianchi
Riccardo
R
Casaccia-Bonnefil
Patrizia
P
Arancio
Ottavio
O
Sap
Jan
J
D000818:Animals; D001522:Behavior, Animal; D002465:Cell Movement; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000166:cytology*; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D018782:Maze Learning; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D011956:Receptors, Cell Surface
D011956:Receptors, Cell Surface; D017027:Protein Tyrosine Phosphatases; C516843:Ptpra protein, mouse; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4