Literature DB >> 30224470

Regulatory γ1 subunits defy symmetry in functional modulation of BK channels.

Vivian Gonzalez-Perez1, Manu Ben Johny2, Xiao-Ming Xia1, Christopher J Lingle3.   

Abstract

Structural symmetry is a hallmark of homomeric ion channels. Nonobligatory regulatory proteins can also critically define the precise functional role of such channels. For instance, the pore-forming subunit of the large conductance voltage and calcium-activated potassium (BK, Slo1, or KCa1.1) channels encoded by a single KCa1.1 gene assembles in a fourfold symmetric fashion. Functional diversity arises from two families of regulatory subunits, β and γ, which help define the range of voltages over which BK channels in a given cell are activated, thereby defining physiological roles. A BK channel can contain zero to four β subunits per channel, with each β subunit incrementally influencing channel gating behavior, consistent with symmetry expectations. In contrast, a γ1 subunit (or single type of γ1 subunit complex) produces a functionally all-or-none effect, but the underlying stoichiometry of γ1 assembly and function remains unknown. Here we utilize two distinct and independent methods, a Forster resonance energy transfer-based optical approach and a functional reporter in single-channel recordings, to reveal that a BK channel can contain up to four γ1 subunits, but a single γ1 subunit suffices to induce the full gating shift. This requires that the asymmetric association of a single regulatory protein can act in a highly concerted fashion to allosterically influence conformational equilibria in an otherwise symmetric K+ channel.

Entities:  

Keywords:  BK channels; FRET; K+ channels; regulatory subunits; stoichiometry

Mesh:

Substances:

Year:  2018        PMID: 30224470      PMCID: PMC6176617          DOI: 10.1073/pnas.1804560115

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


  36 in total

1.  Counting membrane-embedded KCNE beta-subunits in functioning K+ channel complexes.

Authors:  Trevor J Morin; William R Kobertz
Journal:  Proc Natl Acad Sci U S A       Date:  2008-01-25       Impact factor: 11.205

2.  State-dependent FRET reports calcium- and voltage-dependent gating-ring motions in BK channels.

Authors:  Pablo Miranda; Jorge E Contreras; Andrew J R Plested; Fred J Sigworth; Miguel Holmgren; Teresa Giraldez
Journal:  Proc Natl Acad Sci U S A       Date:  2013-03-11       Impact factor: 11.205

3.  Stoichiometry of the cardiac IKs complex.

Authors:  William R Kobertz
Journal:  Proc Natl Acad Sci U S A       Date:  2014-03-28       Impact factor: 11.205

4.  Functional regulation of BK potassium channels by γ1 auxiliary subunits.

Authors:  Vivian Gonzalez-Perez; Xiao-Ming Xia; Christopher J Lingle
Journal:  Proc Natl Acad Sci U S A       Date:  2014-03-17       Impact factor: 11.205

5.  A neuronal beta subunit (KCNMB4) makes the large conductance, voltage- and Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin.

Authors:  P Meera; M Wallner; L Toro
Journal:  Proc Natl Acad Sci U S A       Date:  2000-05-09       Impact factor: 11.205

6.  Generation of functional fluorescent BK channels by random insertion of GFP variants.

Authors:  Teresa Giraldez; Thomas E Hughes; Fred J Sigworth
Journal:  J Gen Physiol       Date:  2005-11       Impact factor: 4.086

7.  Location of modulatory beta subunits in BK potassium channels.

Authors:  Guoxia Liu; Xiaowei Niu; Roland S Wu; Neelesh Chudasama; Yongneng Yao; Xin Jin; Richard Weinberg; Sergey I Zakharov; Howard Motoike; Steven O Marx; Arthur Karlin
Journal:  J Gen Physiol       Date:  2010-04-12       Impact factor: 4.086

8.  Coupling between voltage sensor activation, Ca2+ binding and channel opening in large conductance (BK) potassium channels.

Authors:  Frank T Horrigan; Richard W Aldrich
Journal:  J Gen Physiol       Date:  2002-09       Impact factor: 4.086

9.  The extracellular leucine-rich repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns.

Authors:  Jackie Dolan; Karen Walshe; Samantha Alsbury; Karsten Hokamp; Sean O'Keeffe; Tatsuya Okafuji; Suzanne F C Miller; Guy Tear; Kevin J Mitchell
Journal:  BMC Genomics       Date:  2007-09-14       Impact factor: 3.969

10.  The single transmembrane segment determines the modulatory function of the BK channel auxiliary γ subunit.

Authors:  Qin Li; Xin Guan; Karen Yen; Jiyuan Zhang; Jiusheng Yan
Journal:  J Gen Physiol       Date:  2016-04       Impact factor: 4.086

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  5 in total

Review 1.  Regulation of BK Channels by Beta and Gamma Subunits.

Authors:  Vivian Gonzalez-Perez; Christopher J Lingle
Journal:  Annu Rev Physiol       Date:  2019-02-10       Impact factor: 19.318

Review 2.  The LRRC family of BK channel regulatory subunits: potential roles in health and disease.

Authors:  Vivian Gonzalez-Perez; Yu Zhou; Matthew A Ciorba; Christopher J Lingle
Journal:  J Physiol       Date:  2022-01-24       Impact factor: 5.182

3.  The AMIGO1 adhesion protein activates Kv2.1 voltage sensors.

Authors:  Rebecka J Sepela; Robert G Stewart; Luis A Valencia; Parashar Thapa; Zeming Wang; Bruce E Cohen; Jon T Sack
Journal:  Biophys J       Date:  2022-03-18       Impact factor: 3.699

4.  Regulatory mechanisms of mitochondrial BKCa channels.

Authors:  Ana L González-Cota; Carmen Santana-Calvo; Rocío Servín-Vences; Gerardo Orta; Enrique Balderas
Journal:  Channels (Austin)       Date:  2021-12       Impact factor: 2.581

5.  Variable Assembly of EMRE and MCU Creates Functional Channels with Distinct Gatekeeping Profiles.

Authors:  Riley Payne; Carmen Li; J Kevin Foskett
Journal:  iScience       Date:  2020-04-10
  5 in total

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