Specificity of activation by phosphoinositides determines lipid regulation of Kir channels. Export

@article{citeulike:406608, abstract = {Phosphoinositides are critical regulators of ion channel and transporter activity. Defects in interactions of inwardly rectifying potassium (Kir) channels with phosphoinositides lead to disease. ATP-sensitive K(+) channels (K(ATP)) are unique among Kir channels in that they serve as metabolic sensors, inhibited by ATP while stimulated by long-chain (LC) acyl-CoA. Here we show that K(ATP) are the least specific Kir channels in their activation by phosphoinositides and we demonstrate that LC acyl-CoA activation of these channels depends on their low phosphoinositide specificity. We provide a systematic characterization of phosphoinositide specificity of the entire Kir channel family expressed in Xenopus oocytes and identify molecular determinants of such specificity. We show that mutations in the Kir2.1 channel decreasing phosphoinositide specificity allow activation by LC acyl-CoA. Our data demonstrate that differences in phosphoinositide specificity determine the modulation of Kir channel activity by distinct regulatory lipids.}, address = {Department of Physiology and Biophysics, Mount Sinai School of Medicine of New York University, New York, NY 10029, USA.}, author = {Rohacs, T. and Lopes, C. M. and Jin, T. and Ramdya, P. P. and Moln\'{a}r, Z. and Logothetis, D. E.}, citeulike-article-id = {406608}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0236364100}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/12525701}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=12525701}, day = {21}, doi = {10.1073/pnas.0236364100}, issn = {0027-8424}, journal = {Proc Natl Acad Sci U S A}, keywords = {acyl-coa, coenzyme, inositol, kir, kir11, kir21, kir31, kir62, pip2, pip3, selectivity, specificity}, month = {January}, number = {2}, pages = {745--750}, posted-at = {2005-11-23 19:42:04}, priority = {2}, title = {Specificity of activation by phosphoinositides determines lipid regulation of Kir channels.}, url = {http://dx.doi.org/10.1073/pnas.0236364100}, volume = {100}, year = {2003} }

TY - JOUR ID - citeulike:406608 L3 - citeulike-article-id:406608 N2 - Phosphoinositides are critical regulators of ion channel and transporter activity. Defects in interactions of inwardly rectifying potassium (Kir) channels with phosphoinositides lead to disease. ATP-sensitive K(+) channels (K(ATP)) are unique among Kir channels in that they serve as metabolic sensors, inhibited by ATP while stimulated by long-chain (LC) acyl-CoA. Here we show that K(ATP) are the least specific Kir channels in their activation by phosphoinositides and we demonstrate that LC acyl-CoA activation of these channels depends on their low phosphoinositide specificity. We provide a systematic characterization of phosphoinositide specificity of the entire Kir channel family expressed in Xenopus oocytes and identify molecular determinants of such specificity. We show that mutations in the Kir2.1 channel decreasing phosphoinositide specificity allow activation by LC acyl-CoA. Our data demonstrate that differences in phosphoinositide specificity determine the modulation of Kir channel activity by distinct regulatory lipids. IS - 2 JF - Proc Natl Acad Sci U S A SN - 0027-8424 AD - Department of Physiology and Biophysics, Mount Sinai School of Medicine of New York University, New York, NY 10029, USA. EP - 750 TI - Specificity of activation by phosphoinositides determines lipid regulation of Kir channels. VL - 100 SP - 745 KW - acyl-coa KW - coenzyme KW - inositol KW - kir KW - kir11 KW - kir21 KW - kir31 KW - kir62 KW - pip2 KW - pip3 KW - selectivity KW - specificity AU - Rohacs, T AU - Lopes, CM AU - Jin, T AU - Ramdya, PP AU - Molnár, Z AU - Logothetis, DE PY - 2003/01/21/ UR - http://dx.doi.org/10.1073/pnas.0236364100 ER -