BK potassium channel modulation by leucine-rich repeat-containing proteins
- 30 April 2012
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 109 (20), 7917-7922
- https://doi.org/10.1073/pnas.1205435109
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.Keywords
This publication has 36 references indexed in Scilit:
- LRRC52 (leucine-rich-repeat-containing protein 52), a testis-specific auxiliary subunit of the alkalization-activated Slo3 channelProceedings of the National Academy of Sciences, 2011
- CAPC negatively regulates NF-κB activation and suppresses tumor growth and metastasisOncogene, 2011
- LRRC26 auxiliary protein allows BK channel activation at resting voltage without calciumNature, 2010
- Human leucine-rich repeat proteins: a genome-wide bioinformatic categorization and functional analysis in innate immunityProceedings of the National Academy of Sciences, 2010
- Regulation of Bestrophin Cl Channels by Calcium: Role of the C TerminusThe Journal of general physiology, 2008
- High expression of a cytokeratin-associated protein in many cancersProceedings of the National Academy of Sciences, 2006
- The SWISS-MODEL workspace: a web-based environment for protein structure homology modellingBioinformatics, 2005
- Cloning and Functional Expression of Two Families of β-Subunits of the Large Conductance Calcium-activated K+ ChannelPublished by Elsevier BV ,2000
- hKCNMB3 and hKCNMB4, cloning and characterization of two members of the large‐conductance calcium‐activated potassium channel β subunit familyFEBS Letters, 2000
- Cloning and Functional Characterization of Novel Large Conductance Calcium-activated Potassium Channel β Subunits, hKCNMB3 and hKCNMB4Journal of Biological Chemistry, 2000