title: BK potassium channel modulation by leucine-rich repeat-containing proteins.
abstract: Molecular diversity of ion channel structure and function underlies variability in electrical signaling in nerve, muscle, and nonexcitable cells. Regulation by variable auxiliary subunits is a major mechanism to generate tissue- or cell-specific diversity of ion channel function. Mammalian large-conductance, voltage- and calcium-activated potassium channels (BK, K(Ca)1.1) are ubiquitously expressed with diverse functions in different tissues or cell types, consisting of the pore-forming, voltage- and Ca(2+)-sensing α-subunits (BKα), either alone or together with the tissue-specific auxiliary β-subunits (β1-β4). We recently identified a leucine-rich repeat (LRR)-containing membrane protein, LRRC26, as a BK channel auxiliary subunit, which causes an unprecedented large negative shift (∼140 mV) in voltage dependence of channel activation. Here we report a group of LRRC26 paralogous proteins, LRRC52, LRRC55, and LRRC38 that potentially function as LRRC26-type auxiliary subunits of BK channels. LRRC52, LRRC55, and LRRC38 produce a marked shift in the BK channel's voltage dependence of activation in the hyperpolarizing direction by ∼100 mV, 50 mV, and 20 mV, respectively, in the absence of calcium. They along with LRRC26 show distinct expression in different human tissues: LRRC26 and LRRC38 mainly in secretory glands, LRRC52 in testis, and LRRC55 in brain. LRRC26 and its paralogs are structurally and functionally distinct from the β-subunits and we designate them as a γ family of the BK channel auxiliary proteins, which potentially regulate the channel's gating properties over a spectrum of different tissues or cell types.
authors.affiliation: Section of Neurobiology, Center for Learning and Memory, University of Texas, Austin, TX 78712, USA. jshyan@mail.utexas.edu
authors.forename: Jiusheng
authors.initials: J
authors.lastname: Yan
authors.forename: Richard W
authors.initials: RW
authors.lastname: Aldrich
mesh_terms: D001921:Brain / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D060888:Real-Time Polymerase Chain Reaction; D013737:Testis / Q000378:metabolism
chemical_list: D017931:DNA Primers; C539913:LRRC26 protein, human; C573836:LRRC38 protein, human; C573834:LRRC52 protein, human; C573835:LRRC55 protein, human; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins