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  • The EMBO Journal (2003) 22, 4121 - 4131
  • doi:10.1093/emboj/cdg399

Receptor protein tyrosine phosphatase alpha is essential for hippocampal neuronal migration and long-term potentiation

Angiola Petrone1, Fortunato Battaglia2,3, Cheng Wang1, Adina Dusa1, Jing Su1, David Zagzag4, Riccardo Bianchi5, Patrizia Casaccia-Bonnefil6, Ottavio Arancio2,3,7 and Jan Sap

  1. Department of Pharmacology, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA
  2. Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA
  3. Department of Psychiatry, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA
  4. Department of Pathology, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA
  5. Department of Physiology and Pharmacology, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA
  6. Department of Neuroscience and Cell Biology, UMDNJ, Piscataway, NJ 08854, USA
  7. Department of Physiology and Neuroscience, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA

Correspondence to:

Jan Sap, E-mail: jan.sap@med.nyu.edu

Received 6 December 2002; Accepted 25 June 2003; Revised 12 June 2003

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.

  • Keywords:

    • hippocampus,
    • neuronal migration,
    • plasticity,
    • RPTPalpha,
    • tyrosine phosphatase