Direct activation of trpl cation channels by Gα11 subunits

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.