Get access

Involvement of protein-tyrosine phosphatase PTPMEG in motor learning and cerebellar long-term depression

Authors

  • Shin-ichiro Kina,

    1. Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, 108-8639, Japan
    Search for more papers by this author
  • Tohru Tezuka,

    1. Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, 108-8639, Japan
    Search for more papers by this author
  • Shinji Kusakawa,

    1. Division of Neuronal Network, Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, 108-8639, Japan
    Search for more papers by this author
  • Yasushi Kishimoto,

    1. Department of Cellular Neurophysiology, Graduate School of Medical Science, Kanazawa University, Kanazawa, 920-8640, Japan
    2. Department of Cellular Neuroscience, Graduate School of Medicine, Osaka University, Suita, 565-0871, Japan
    Search for more papers by this author
    • *

      Present address: Department of Neurobiophysics, Graduate School of Pharmaceutical Sciences at Kagawa campus, Tokushima Bunri University, Sanuki, 769-2193, Japan.

  • Sho Kakizawa,

    1. Department of Cellular and Molecular Pharmacology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, 113-0033, Japan
    Search for more papers by this author
  • Koichi Hashimoto,

    1. Department of Cellular Neurophysiology, Graduate School of Medical Science, Kanazawa University, Kanazawa, 920-8640, Japan
    2. Department of Cellular Neuroscience, Graduate School of Medicine, Osaka University, Suita, 565-0871, Japan
    Search for more papers by this author
  • Miho Ohsugi,

    1. Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, 108-8639, Japan
    Search for more papers by this author
  • Yuji Kiyama,

    1. Division of Neuronal Network, Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, 108-8639, Japan
    Search for more papers by this author
  • Reiko Horai,

    1. Division of Cell Biology, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, 108-8639, Japan
    Search for more papers by this author
  • Katsuko Sudo,

    1. Division of Cell Biology, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, 108-8639, Japan
    Search for more papers by this author
    • Present address: Animal Research Center, Tokyo Medical University, Tokyo, 160-8402, Japan.

  • Shigeru Kakuta,

    1. Division of Cell Biology, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, 108-8639, Japan
    Search for more papers by this author
  • Yoichiro Iwakura,

    1. Division of Cell Biology, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, 108-8639, Japan
    Search for more papers by this author
  • Masamitsu Iino,

    1. Department of Cellular and Molecular Pharmacology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, 113-0033, Japan
    Search for more papers by this author
  • Masanobu Kano,

    1. Department of Cellular Neurophysiology, Graduate School of Medical Science, Kanazawa University, Kanazawa, 920-8640, Japan
    2. Department of Cellular Neuroscience, Graduate School of Medicine, Osaka University, Suita, 565-0871, Japan
    Search for more papers by this author
  • Toshiya Manabe,

    1. Division of Neuronal Network, Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, 108-8639, Japan
    2. CREST and RISTEX, Japan Science and Technology Agency
    Search for more papers by this author
  • Tadashi Yamamoto

    1. Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, 108-8639, Japan
    Search for more papers by this author

Dr T. Yamamoto, as above.
E-mail: tyamamot@ims.u-tokyo.ac.jp

Abstract

Although protein-tyrosine phosphorylation is important for hippocampus-dependent learning, its role in cerebellum-dependent learning remains unclear. We previously found that PTPMEG, a cytoplasmic protein-tyrosine phosphatase expressed in Purkinje cells (PCs), bound to the carboxyl-terminus of the glutamate receptor δ2 via the postsynaptic density-95/discs-large/ZO-1 domain of PTPMEG. In the present study, we generated PTPMEG-knockout (KO) mice, and addressed whether PTPMEG is involved in cerebellar plasticity and cerebellum-dependent learning. The structure of the cerebellum in PTPMEG-KO mice appeared grossly normal. However, we found that PTPMEG-KO mice showed severe impairment in the accelerated rotarod test. These mice also exhibited impairment in rapid acquisition of the cerebellum-dependent delay eyeblink conditioning, in which conditioned stimulus (450-ms tone) and unconditioned stimulus (100-ms periorbital electrical shock) were co-terminated. Moreover, long-term depression at parallel fiber–PC synapses was significantly attenuated in these mice. Developmental elimination of surplus climbing fibers and the physiological properties of excitatory synaptic inputs to PCs appeared normal in PTPMEG-KO mice. These results suggest that tyrosine dephosphorylation events regulated by PTPMEG are important for both motor learning and cerebellar synaptic plasticity.

Ancillary