Direct activation of trpl cation channels by G alpha11 subunits.
G proteins of the Gq/11 subfamily functionally couple cell surface receptors to phospholipase C beta (PLC beta) isoforms. Stimulation of PLC beta induces Ca2+ elevation by inositol 1,4,5-trisphosphate (InsP3)-mediated Ca2+ release and store-dependent 'capacitative' Ca2+ entry through Ca(2+)-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 Ca(2+)-permeable cation channel, but is not activated by store depletion. Co-expression of the constitutively active Gq subfamily member G alpha 11 (G alpha 11) with trpl enhanced trpl currents 33-fold in comparison with co-expression of trpl with other G alpha isoforms or G beta gamma complexes. This activation could not be attributed to signals downstream of PLC beta. In particular, InsP3 infusion, modulation of protein kinase C activity or elevation of intracellular calcium concentration failed to induce trpl currents. In contrast, purified G alpha 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 Gq subfamily may induce Ca2+ entry not only indirectly via store-operated mechanisms but also by directly stimulating cation channels.
Obukhov
A G
AG
Institut für Pharmakologie, Freie Universität Berlin, Germany.
Harteneck
C
C
Zobel
A
A
Harhammer
R
R
Kalkbrenner
F
F
Leopoldt
D
D
Lückhoff
A
A
Nürnberg
B
B
Schultz
G
G
D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D029721:Drosophila Proteins; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D018411:Spodoptera; D050051:Transient Receptor Potential Channels
D002148:Calmodulin-Binding Proteins; D029721:Drosophila Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D011994:Recombinant Proteins; D050051:Transient Receptor Potential Channels; C074192:trpl protein, Drosophila; D019204:GTP-Binding Proteins; D002118:Calcium