STIM1-dependent and STIM1-independent Function of Transient Receptor Potential Canonical (TRPC) Channels Tunes Their Store-operated Mode

Ca(2+)influx by store-operated Ca2+ channels is a key component of the receptor-evoked Ca2+ signal. In all cells examined, transient receptor potential canonical (TRPC) channels mediate a significant portion of the receptor-stimulated Ca2+ influx. Recent studies have revealed how STIM1 activates TRPC1 in response to store depletion; however, the role of STIM1 in TRPC channel activation by receptor stimulation is not fully understood. Here, we established mutants of TRPC channels that could not be activated by STIM1 but were activated by the "charge-swap" mutant STIM1(K684E,K685E). Significantly, WT but not mutant TRPC channels were inhibited by scavenging STIM1 with Orai1(R91W), indicating the STIM1 dependence and independence of WT and mutant TRPC channels, respectively. Importantly, mutant TRPC channels were robustly activated by receptor stimulation. Moreover, STIM1 and STIM1(K684E, K685E) reciprocally affected receptor-activated WT and mutant TRPC channels. Together, these findings indicate that TRPC channels can function as STIM1-dependent and STIM1-independent channels, which increases the versatility of TRPC channel function and their role in receptor-stimulated Ca2+ influx.This work was supported, in whole or in part, by National Institutes of Health Grants DE12302 and DK38938 and by NIDCR/DIR.Park CY, 2009, CELL, V136, P876, DOI 10.1016/j.cell.2009.02.014Liao YY, 2009, P NATL ACAD SCI USA, V106, P3202, DOI 10.1073/pnas.0813346106Yuan JP, 2009, NAT CELL BIOL, V11, P337, DOI 10.1038/ncb1842Zeng WZ, 2008, MOL CELL, V32, P439, DOI 10.1016/j.molcel.2008.09.020DeHaven WI, 2008, J BIOL CHEM, V283, P19265, DOI 10.1074/jbc.M801535200Muik M, 2008, J BIOL CHEM, V283, P8014, DOI 10.1074/jbc.M708898200Yuan JP, 2007, NAT CELL BIOL, V9, P636, DOI 10.1038/ncb1590Liou J, 2007, P NATL ACAD SCI USA, V104, P9301, DOI 10.1073/pnas.0702866104Nilius B, 2007, PHYSIOL REV, V87, P165, DOI 10.1152/physrev.00021.2006Kim MS, 2009, J BIOL CHEM, V284, P9733, DOI 10.1074/jbc.M808097200Kawasaki T, 2009, BIOCHEM BIOPH RES CO, V385, P49, DOI 10.1016/j.bbrc.2009.05.020Lee KP, 2009, P NATL ACAD SCI USA, V106, P14687, DOI 10.1073/pnas.0904664106Mullins FM, 2009, P NATL ACAD SCI USA, V106, P15495, DOI 10.1073/pnas.0906781106Derler I, 2009, J BIOL CHEM, V284, P24933, DOI 10.1074/jbc.C109.024083Lee KP, 2010, FEBS LETT, V584, P2022, DOI 10.1016/j.febslet.2009.11.078Stathopulos PB, 2006, J BIOL CHEM, V281, P35855, DOI 10.1074/jbc.M608247200Lalioti MD, 2006, NAT GENET, V38, P1124, DOI 10.1038/ng1877Wu MM, 2006, J CELL BIOL, V174, P803Huang GN, 2006, NAT CELL BIOL, V8, P1003, DOI 10.1038/ncb1454Mercer JC, 2006, J BIOL CHEM, V281, P24979, DOI 10.1074/jbc.M604589200Peinelt C, 2006, NAT CELL BIOL, V8, P771, DOI 10.1038/ncb1435Vig M, 2006, SCIENCE, V312, P1220, DOI 10.1126/science.1127883Feske S, 2006, NATURE, V441, P179, DOI 10.1038/nature04702Liou J, 2005, CURR BIOL, V15, P1235, DOI 10.1016/j.cub.2005.05.055Roos J, 2005, J CELL BIOL, V169, P435, DOI 10.1093/jcb.200502019Parekh AB, 2005, PHYSIOL REV, V85, P757, DOI 10.1152/physrev.00057.2003