Palmitoylation of the S0-S1 Linker Regulates Cell Surface Expression of Voltage- and Calcium-activated Potassium (BK) Channels
| Autor: | Iain Rowe, Heather McClafferty, Nina Geiger, H.-G. Knaus, Owen Jeffries, Lijun Tian, Peter Ruth, Danlei Bi, Michael J. Shipston, Lie Chen |
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| Rok vydání: | 2010 |
| Předmět: |
BK channel
Potassium Channels Palmitic Acid Membrane trafficking Biochemistry Ion Channels Cell membrane Mice 0302 clinical medicine Membrane proteins Protein palmitoylation 0303 health sciences biology Chemistry Potassium channel Cell biology Transmembrane domain medicine.anatomical_structure Ion channels lipids (amino acids peptides and proteins) Signal Transduction Mutation Missense Potassium channels Cell Line 03 medical and health sciences Palmitoylation Membrane Biology medicine Animals Humans Large-Conductance Calcium-Activated Potassium Channels Molecular Biology Ion channel 030304 developmental biology Cell Membrane technology industry and agriculture Membrane Proteins Cell Biology Protein Structure Tertiary Alternative Splicing Protein Palmitoylation Amino Acid Substitution Gene Expression Regulation Membrane Trafficking biology.protein Protein Processing Post-Translational Linker 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Biological Chemistry Jeffries, O, Geiger, N, Rowe, I C M, Tian, L J, McClafferty, H, Chen, L, Bi, D L, Knaus, H G, Ruth, P & Shipston, M J 2010, ' Palmitoylation of the S0-S1 Linker Regulates Cell Surface Expression of Voltage-and Calcium-activated Potassium (BK) Channels ', Journal of Biological Chemistry, vol. 285, no. 43, pp. 33307-33314 . https://doi.org/10.1074/jbc.M110.153940 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m110.153940 |
| Popis: | S-Palmitoylation is rapidly emerging as an important post-translational mechanism to regulate ion channels. We have previously demonstrated that large conductance calcium-and voltage-activated potassium (BK) channels are palmitoylated within an alternatively spliced (STREX) insert. However, these studies also revealed that additional site(s) for palmitoylation must exist outside of the STREX insert, although the identity or the functional significance of these palmitoylated cysteine residues are unknown. Here, we demonstrate that BK channels are palmitoylated at a cluster of evolutionary conserved cysteine residues (Cys-53, Cys-54, and Cys-56) within the intracellular linker between the S0 and S1 transmembrane domains. Mutation of Cys-53, Cys-54, and Cys-56 completely abolished palmitoylation of BK channels lacking the STREX insert (ZERO variant). Palmitoylation allows the S0-S1 linker to associate with the plasma membrane but has no effect on single channel conductance or the calcium/voltage sensitivity. Rather, S0-S1 linker palmitoylation is a critical determinant of cell surface expression of BK channels, as steady state surface expression levels are reduced by similar to 55% in the C53:54:56 A mutant. STREX variant channels that could not be palmitoylated in the S0-S1 linker also displayed significantly reduced cell surface expression even though STREX insert palmitoylation was unaffected. Thus our work reveals the functional independence of two distinct palmitoylation-dependent membrane interaction domains within the same channel protein and demonstrates the critical role of S0-S1 linker palmitoylation in the control of BK channel cell surface expression. |
| Databáze: | OpenAIRE |
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