TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade

  • Chieko Koike
    Departments of aDevelopmental Biology and
  • Takehisa Obara
    Department of Psychology, Graduate School of Humanities and Sociology, University of Tokyo, Tokyo 113-0033, Japan;
  • Yoshitsugu Uriu
    Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan;
  • Tomohiro Numata
    Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan;
  • Rikako Sanuki
    Departments of aDevelopmental Biology and
  • Kentarou Miyata
    Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; and
  • Toshiyuki Koyasu
    Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; and
  • Shinji Ueno
    Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; and
  • Kazuo Funabiki
    Systems Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan;
  • Akiko Tani
    Departments of aDevelopmental Biology and
  • Hiroshi Ueda
    Department of Biomolecular Science, Faculty of Engineering, Gifu University, Gifu 501-1193, Japan
  • Mineo Kondo
    Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; and
  • Yasuo Mori
    Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan;
  • Masao Tachibana
    Department of Psychology, Graduate School of Humanities and Sociology, University of Tokyo, Tokyo 113-0033, Japan;
  • Takahisa Furukawa
    Departments of aDevelopmental Biology and

説明

<jats:p>An essential step in intricate visual processing is the segregation of visual signals into ON and OFF pathways by retinal bipolar cells (BCs). Glutamate released from photoreceptors modulates the photoresponse of ON BCs via metabotropic glutamate receptor 6 (mGluR6) and G protein (Go) that regulates a cation channel. However, the cation channel has not yet been unequivocally identified. Here, we report a mouse TRPM1 long form (TRPM1-L) as the cation channel. We found that TRPM1-L localization is developmentally restricted to the dendritic tips of ON BCs in colocalization with mGluR6. TRPM1 null mutant mice completely lose the photoresponse of ON BCs but not that of OFF BCs. In the TRPM1-L-expressing cells, TRPM1-L functions as a constitutively active nonselective cation channel and its activity is negatively regulated by Go in the mGluR6 cascade. These results demonstrate that TRPM1-L is a component of the ON BC transduction channel downstream of mGluR6 in ON BCs.</jats:p>

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