BK potassium channel modulation by leucine-rich repeat-containing proteins.
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Yan J, Aldrich RW
BK potassium channel modulation by leucine-rich repeat-containing proteins.
Proc Natl Acad Sci U S A. 2012 May 15;109(20):7917-22. doi: 10.1073/pnas.1205435109. Epub 2012 Apr 30.
- PubMed ID
- 22547800 [ View in PubMed]
- 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 alpha-subunits (BKalpha), either alone or together with the tissue-specific auxiliary beta-subunits (beta1-beta4). 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 ( approximately 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 approximately 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 beta-subunits and we designate them as a gamma family of the BK channel auxiliary proteins, which potentially regulate the channel's gating properties over a spectrum of different tissues or cell types.