title: Receptor protein tyrosine phosphatase alpha is essential for hippocampal neuronal migration and long-term potentiation.
abstract: 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.
authors.affiliation: Department of Pharmacology, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA.
authors.forename: Angiola
authors.initials: A
authors.lastname: Petrone
authors.forename: Fortunato
authors.initials: F
authors.lastname: Battaglia
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Adina
authors.initials: A
authors.lastname: Dusa
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.forename: David
authors.initials: D
authors.lastname: Zagzag
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bianchi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Casaccia-Bonnefil
authors.forename: Ottavio
authors.initials: O
authors.lastname: Arancio
authors.forename: Jan
authors.initials: J
authors.lastname: Sap
mesh_terms: 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
chemical_list: D011956:Receptors, Cell Surface; D017027:Protein Tyrosine Phosphatases; C516843:Ptpra protein, mouse; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4