Palmitoylation of the β4-Subunit Regulates Surface Expression of Large Conductance Calcium-activated Potassium Channel Splice Variants*
| Autor: | H.-G. Knaus, Lie Chen, Heather McClafferty, Michael J. Shipston, Lijun Tian, Peter Ruth, Franziska Steeb, Danlei Bi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
BK channel
Potassium Channels Lipoylation Amino Acid Motifs Endoplasmic Reticulum Biochemistry Ion Channels 03 medical and health sciences 0302 clinical medicine Palmitoylation Membrane Biology Animals Humans Protein Isoforms Protein palmitoylation Large-Conductance Calcium-Activated Potassium Channels Molecular Biology 030304 developmental biology 0303 health sciences biology Endoplasmic reticulum S-acylation Cell Biology 16. Peace & justice Calcium-activated potassium channel Cell biology Protein Palmitoylation Protein Subunits Protein Transport HEK293 Cells Membrane Transport Gene Expression Regulation biology.protein S-Acylation Signal transduction Protein Processing Post-Translational 030217 neurology & neurosurgery Intracellular Signal Transduction |
| Zdroj: | The Journal of Biological Chemistry Chen, L, Bi, D, Tian, L, McClafferty, H, Steeb, F, Ruth, P, Knaus, H G & Shipston, M J 2013, ' Palmitoylation of the β4-Subunit Regulates Surface Expression of Large Conductance Calcium-activated Potassium Channel Splice Variants ', Journal of Biological Chemistry, vol. 288, no. 18, pp. 13136-13144 . https://doi.org/10.1074/jbc.M113.461830 |
| ISSN: | 1083-351X 0021-9258 |
| DOI: | 10.1074/jbc.M113.461830 |
| Popis: | Background: The role of post-translational modification of regulatory β-subunits in the control of large conductance potassium (BK) channels is largely unknown. Results: β4-subunit palmitoylation controls surface trafficking of BK channel α-subunit splice variants. Conclusion: Palmitoylation of β4 masks an α-subunit trafficking motif to control surface delivery. Significance: Palmitoylation of regulatory subunits provides a dynamic mechanism to control surface trafficking of specific BK channel variants. Regulatory β-subunits of large conductance calcium- and voltage-activated potassium (BK) channels play an important role in generating functional diversity and control of cell surface expression of the pore forming α-subunits. However, in contrast to α-subunits, the role of reversible post-translational modification of intracellular residues on β-subunit function is largely unknown. Here we demonstrate that the human β4-subunit is S-acylated (palmitoylated) on a juxtamembrane cysteine residue (Cys-193) in the intracellular C terminus of the regulatory β-subunit. β4-Subunit palmitoylation is important for cell surface expression and endoplasmic reticulum (ER) exit of the β4-subunit alone. Importantly, palmitoylated β4-subunits promote the ER exit and surface expression of the pore-forming α-subunit, whereas β4-subunits that cannot be palmitoylated do not increase ER exit or surface expression of α-subunits. Strikingly, however, this palmitoylation- and β4-dependent enhancement of α-subunit surface expression was only observed in α-subunits that contain a putative trafficking motif (… REVEDEC) at the very C terminus of the α-subunit. Engineering this trafficking motif to other C-terminal α-subunit splice variants results in α-subunits with reduced surface expression that can be rescued by palmitoylated, but not depalmitoylated, β4-subunits. Our data reveal a novel mechanism by which palmitoylated β4-subunit controls surface expression of BK channels through masking of a trafficking motif in the C terminus of the α-subunit. As palmitoylation is dynamic, this mechanism would allow precise control of specific splice variants to the cell surface. Our data provide new insights into how complex interplay between the repertoire of post-transcriptional and post-translational mechanisms controls cell surface expression of BK channels. |
| Databáze: | OpenAIRE |
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