title: Distinct domains of the β1-subunit cytosolic N terminus control surface expression and functional properties of large-conductance calcium-activated potassium (BK) channels.
abstract: The properties and function of large-conductance calcium- and voltage-activated potassium (BK) channels are modified by the tissue-specific expression of regulatory β1-subunits. Although the short cytosolic N-terminal domain of the β1-subunit is important for controlling both BK channel trafficking and function, whether the same, or different, regions of the N terminus control these distinct processes remains unknown. Here we demonstrate that the first six N-terminal residues including Lys-3, Lys-4, and Leu-5 are critical for controlling functional regulation, but not trafficking, of BK channels. This membrane-distal region has features of an amphipathic helix that is predicted to control the orientation of the first transmembrane-spanning domain (TM1) of the β1-subunit. In contrast, a membrane-proximal leucine residue (Leu-17) controls trafficking without affecting functional coupling, an effect that is in part dependent on controlling efficient endoplasmic reticulum exit of the pore-forming α-subunit. Thus cell surface trafficking and functional coupling with BK channels are controlled by distinct domains of the β1-subunit N terminus.
authors.affiliation: From the Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH8 9XD, Scotland, United Kingdom.|PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam, Jalan Tungku Link BE1410, Brunei Darussalam.
authors.forename: Lie
authors.initials: L
authors.lastname: Chen
authors.affiliation: From the Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH8 9XD, Scotland, United Kingdom.|Neurodegenerative Disease Research Center, School of Life Sciences, University of Science and Technology of China, Hefei 230026, China,and.
authors.forename: Danlei
authors.initials: D
authors.lastname: Bi
authors.affiliation: PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam, Jalan Tungku Link BE1410, Brunei Darussalam.|Division of Genetics and Genomics, The Roslin Institute, University of Edinburgh, Edinburgh EH25 9RG, Scotland, United Kingdom.
authors.forename: Zen Huat
authors.initials: ZH
authors.lastname: Lu
authors.affiliation: From the Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH8 9XD, Scotland, United Kingdom.
authors.forename: Heather
authors.initials: H
authors.lastname: McClafferty
authors.affiliation: From the Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH8 9XD, Scotland, United Kingdom, mike.shipston@ed.ac.uk.
authors.forename: Michael J
authors.identifier: 0000-0001-7544-582X
authors.initials: MJ
authors.lastname: Shipston
mesh_terms: D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000096:biosynthesis* / Q000235:genetics; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000096:biosynthesis* / Q000235:genetics; D000072417:Protein Domains; D021381:Protein Transport / Q000502:physiology
chemical_list: C494841:KCNMA1 protein, human; C531905:KCNMB1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits
keywords: channel activation; electrophysiology; membrane trafficking; membrane transport; potassium channel