TY - JOUR
T1 - Functional properties of a pore mutant in the Drosophila melanogaster inositol 1,4,5-trisphosphate receptor
AU - Srikanth, Sonal
AU - Wang, Zhengnan
AU - Hasan, Gaiti
AU - Bezprozvanny, Ilya
N1 - Funding Information:
S.S.'s visit to Dallas was supported by J. Cell Science travelling fellowship. I.B. is supported by the Robert A. Welch Foundation and NIH R01 NS38082. G.H. is supported by a grant from the Department of Science and Technology and core grants from the National Centre for Biological Sciences, TIFR, Bangalore.
PY - 2004/9/24
Y1 - 2004/9/24
N2 - The inositol (1,4,5)-trisphosphate receptor (InsP3R) is an intracellular calcium release channel that plays a crucial role in cell signaling. In Drosophila melanogaster, a single InsP3R gene (itpr) encodes a protein (DmInsP3R) that is ∼60% conserved with mammalian InsP3Rs. The functional properties of wild-type (WT) and mutant DmInsP3Rs have recently been described [Srikanth et al., Biophys. J. 86 (2004) 3634-3646]. Here, we use the planar lipid bilayer reconstitution technique to describe single channel properties of a ka901 point mutant (G2630S) in the pore-forming region of DmInsP3R. We find that homomeric ka901 channels are not functional, but the heteromeric WT:ka901 mutant channels display increased conductance, longer channel open time and altered ion selectivity properties when compared to WT DmInsP3R. Obtained results are consistent with the gain of function phenotype observed in ka901/+ mutant flies.
AB - The inositol (1,4,5)-trisphosphate receptor (InsP3R) is an intracellular calcium release channel that plays a crucial role in cell signaling. In Drosophila melanogaster, a single InsP3R gene (itpr) encodes a protein (DmInsP3R) that is ∼60% conserved with mammalian InsP3Rs. The functional properties of wild-type (WT) and mutant DmInsP3Rs have recently been described [Srikanth et al., Biophys. J. 86 (2004) 3634-3646]. Here, we use the planar lipid bilayer reconstitution technique to describe single channel properties of a ka901 point mutant (G2630S) in the pore-forming region of DmInsP3R. We find that homomeric ka901 channels are not functional, but the heteromeric WT:ka901 mutant channels display increased conductance, longer channel open time and altered ion selectivity properties when compared to WT DmInsP3R. Obtained results are consistent with the gain of function phenotype observed in ka901/+ mutant flies.
KW - DmInsPR, Drosophila melsanogaster inositol 1,4,5 trisphosphate receptor
KW - Inositol (1,4,5)-trisphosphate receptor
KW - Planar lipid bilayer
KW - RyanR, ryanodine receptor
KW - Single channel recording
KW - Structure-function
KW - WT, wild-type
UR - http://www.scopus.com/inward/record.url?scp=4544315705&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4544315705&partnerID=8YFLogxK
U2 - 10.1016/j.febslet.2004.08.042
DO - 10.1016/j.febslet.2004.08.042
M3 - Article
C2 - 15388340
AN - SCOPUS:4544315705
SN - 0014-5793
VL - 575
SP - 95
EP - 98
JO - FEBS Letters
JF - FEBS Letters
IS - 1-3
ER -