title: Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies.
abstract: Inwardly rectifying K(+) (Kir) channels are important regulators of resting membrane potential and cell excitability. The activity of Kir channels is critically dependent on the integrity of channel interactions with phosphatidylinositol 4,5-bisphosphate (PIP(2)). Here we identify and characterize channel-PIP(2) interactions that are conserved among Kir family members. We find basic residues that interact with PIP(2), two of which have been associated with Andersen's and Bartter's syndromes. We show that several naturally occurring mutants decrease channel-PIP(2) interactions, leading to disease.
authors.affiliation: Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA.
authors.forename: Coeli M B
authors.initials: CM
authors.lastname: Lopes
authors.forename: Hailin
authors.initials: H
authors.lastname: Zhang
authors.forename: Tibor
authors.initials: T
authors.lastname: Rohacs
authors.forename: Taihao
authors.initials: T
authors.lastname: Jin
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Diomedes E
authors.initials: DE
authors.lastname: Logothetis
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001477:Bartter Syndrome / Q000235:genetics / Q000378:metabolism; D017124:Conserved Sequence / Q000235:genetics*; D005260:Female; D006011:Glycogen Storage Disease Type IV / Q000235:genetics / Q000378:metabolism; D015640:Ion Channel Gating / Q000235:genetics; D008564:Membrane Potentials / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009865:Oocytes / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics* / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D019269:Phosphatidylinositol 4,5-Diphosphate; D024661:Potassium Channels, Inwardly Rectifying