Direct activation of trpl cation channels by Gα11 subunits

Alexander G. Obukhov, Christian Harteneck, Andrea Zobel, Rainer Harhammer, Frank Kalkbrenner, Daniela Leopoldt, Andreas Lückhoff, Bernd Nürnberg, Günter Schultz

Research output: Contribution to journalArticle

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Abstract

G proteins of the G(q/11) subfamily functionally couple cell surface receptors to phospholipase C β (PLC β) isoforms. Stimulation of PLC β induces Ca2+ elevation by inositol 1,4,5-trisphosphate (InsP3)-mediated Ca2+ release and store-dependent 'capacitative' Ca2+ entry through Ca2+-permeable channels. The Drosophila trp gene, as well as some human trp homologs, code for such store-operated channels. The related trp-like (trpl) gene product also forms a Ca2+-permeable cation channel, but is not activated by store depletion. Co-expression of the constitutively active G(q) subfamily member Gα11 (Gα(*)11) with trpl enhanced trpl currents 33-fold in comparison with co-expression of trpl with other Gα isoforms or Gβγ complexes. This activation could not be attributed to signals downstream of PLC β. In particular, InsP3 infusion, modulation of protein kinase C activity or elevation of intracellular calcium concentration failed to induce trpl currents. In contrast, purified Gα(*)11 (but not other G protein subunits) activated trpl channels in inside-out patches. We conclude that trpl is regulated by G11 proteins in a membrane-confined manner not involving cytosolic factors. Thus, G proteins of the G(q) subfamily may induce Ca2+ entry not only indirectly via store-operated mechanisms but also by directly stimulating cation channels.

Original languageEnglish (US)
Pages (from-to)5833-5838
Number of pages6
JournalEMBO Journal
Volume15
Issue number21
StatePublished - Nov 1 1996

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Keywords

  • G proteins
  • Ion channels
  • Signal transduction

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Obukhov, A. G., Harteneck, C., Zobel, A., Harhammer, R., Kalkbrenner, F., Leopoldt, D., Lückhoff, A., Nürnberg, B., & Schultz, G. (1996). Direct activation of trpl cation channels by Gα11 subunits. EMBO Journal, 15(21), 5833-5838.