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Regulation of Ca2+ channel expression at the cell surface by the small G-protein kir/Gem

Author

Listed:
  • Pascal Béguin

    (Graduate School of Medicine, Chiba University
    Institut de Pharmacologie et de Toxicologie de l'Université de Lausanne)

  • Kazuaki Nagashima

    (Graduate School of Medicine, Chiba University)

  • Tohru Gonoi

    (Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, 1-8-1)

  • Tadao Shibasaki

    (Graduate School of Medicine, Chiba University)

  • Kazuo Takahashi

    (Core Research for Evolutional Science and Technology (CREST), Graduate School of Medicine, Chiba University)

  • Yasushige Kashima

    (Graduate School of Medicine, Chiba University)

  • Nobuaki Ozaki

    (Graduate School of Medicine, Chiba University)

  • Käthi Geering

    (Institut de Pharmacologie et de Toxicologie de l'Université de Lausanne)

  • Toshihiko Iwanaga

    (Laboratory of Anatomy, Graduate School of Veterinary Medicine, Hokkaido University)

  • Susumu Seino

    (Graduate School of Medicine, Chiba University)

Abstract

Voltage-dependent calcium (Ca2+) channels are involved in many specialized cellular functions1,2,3, and are controlled by intracellular signals such as heterotrimeric G-proteins4, protein kinases5,6 and calmodulin (CaM)7,8. However, the direct role of small G-proteins in the regulation of Ca2+ channels is unclear. We report here that the GTP-bound form of kir/Gem, identified originally as a Ras-related small G-protein that binds CaM9,10,11, inhibits high-voltage-activated Ca2+ channel activities by interacting directly with the β-subunit. The reduced channel activities are due to a decrease in α1-subunit expression at the plasma membrane. The binding of Ca2+/CaM to kir/Gem is required for this inhibitory effect by promoting the cytoplasmic localization of kir/Gem. Inhibition of L-type Ca2+ channels by kir/Gem prevents Ca2+-triggered exocytosis in hormone-secreting cells. We propose that the small G-protein kir/Gem, interacting with β-subunits, regulates Ca2+ channel expression at the cell surface.

Suggested Citation

  • Pascal Béguin & Kazuaki Nagashima & Tohru Gonoi & Tadao Shibasaki & Kazuo Takahashi & Yasushige Kashima & Nobuaki Ozaki & Käthi Geering & Toshihiko Iwanaga & Susumu Seino, 2001. "Regulation of Ca2+ channel expression at the cell surface by the small G-protein kir/Gem," Nature, Nature, vol. 411(6838), pages 701-706, June.
    • Handle: RePEc:nat:nature:v:411:y:2001:i:6838:d:10.1038_35079621
    DOI: 10.1038/35079621
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    Cited by:

    1. Travis J. Morgenstern & Neha Nirwan & Erick O. Hernández-Ochoa & Hugo Bibollet & Papiya Choudhury & Yianni D. Laloudakis & Manu Johny & Roger A. Bannister & Martin F. Schneider & Daniel L. Minor & Hen, 2022. "Selective posttranslational inhibition of CaVβ1-associated voltage-dependent calcium channels with a functionalized nanobody," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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