Phospholipase Cβ4 and Protein Kinase Cα and/or Protein Kinase CβI Are Involved in the Induction of Long Term Depression in Cerebellar Purkinje Cells

Moritoshi Hirono, Takashi Sugiyama, Yasushi Kishimoto, Ikuko Sakai, Takahito Miyazawa, Masahiro Kishio, Hiroko Inoue, Kazuki Nakao, Masayuki Ikeda, Shigenori Kawahara, Yutaka Kirino, Motoya Katsuki, Hidenori Horie, Yoshihiro Ishikawa, Tohru Yoshioka

    Research output: Contribution to journalArticlepeer-review

    55 Citations (Scopus)

    Abstract

    Activation of the type-1 metabotropic glutamate receptor (mGluR1) signaling pathway in the cerebellum involves activation of phospholipase C (PLC) and protein kinase C (PKC) for the induction of cerebellar long term depression (LTD). The PLC and PKC isoforms that are involved in LTD remain unclear, however. One previous study found no change in LTD in PKCγ-deficient mice, thus, in the present study, we examined cerebellar LTD in PLCβ4-deficient mice. Immunohistochemical and Western blot analyses of cerebellum from wild-type mice revealed that PLCβ1 was expressed weakly and uniformly, PLCβ2 was not detected, PLCβ3 was expressed predominantly in caudal cerebellum (lobes 7-10), and PLCβ4 was expressed uniformly throughout. In PLCβ4-deficient mice, expression of total PLCβ, the mGluR1-mediated Ca2+ response, and LTD induction were greatly reduced in rostral cerebellum (lobes 1-6). Furthermore, we used immunohistochemistry to localize PKCα, -βI, -βII, and -γ in mouse cerebellar Purkinje cells during LTD induction. Both PKCα and PKCβI were found to be translocated to the plasmamembrane under these conditions. Taken together, these results suggest that mGluR1-mediated activation of PLCβ4 in rostral cerebellar Purkinje cells induced LTD via PKCα and/or PKCβI.

    Original languageEnglish
    Pages (from-to)45236-45242
    Number of pages7
    JournalJournal of Biological Chemistry
    Volume276
    Issue number48
    DOIs
    Publication statusPublished - 2001 Nov 30

    ASJC Scopus subject areas

    • Biochemistry

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