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Membrane trafficking of large conductance calcium-activated potassium channels is regulated by alternative splicing of a transplantable, acidic trafficking motif in the RCK1-RCK2 linker
- Source :
- The Journal of Biological Chemistry, Chen, L, Jeffries, O, Rowe, I C M, Liang, Z, Knaus, H G, Ruth, P & Shipston, M J 2010, ' Membrane Trafficking of Large Conductance Calcium-activated Potassium Channels Is Regulated by Alternative Splicing of a Transplantable, Acidic Trafficking Motif in the RCK1-RCK2 Linker ', Journal of Biological Chemistry, vol. 285, no. 30, pp. 23263-23273 . https://doi.org/10.1074/jbc.M110.139758
- Publication Year :
- 2010
- Publisher :
- Elsevier, 2010.
-
Abstract
- Trafficking of the pore-forming alpha-subunits of large conductance calcium-and voltage-activated potassium (BK) channels to the cell surface represents an important regulatory step in controlling BK channel function. Here, we identify multiple trafficking signals within the intracellular RCK1-RCK2 linker of the cytosolic C terminus of the channel that are required for efficient cell surface expression of the channel. In particular, an acidic cluster-like motif was essential for channel exit from the endoplasmic reticulum and subsequent cell surface expression. This motif could be transplanted onto a heterologous nonchannel protein to enhance cell surface expression by accelerating endoplasmic reticulum export. Importantly, we identified a human alternatively spliced BK channel variant, hSlo Delta(579-664), in which these trafficking signals are excluded because of in-frame exon skipping. The hSlo Delta(579-664) variant is expressed in multiple human tissues and cannot form functional channels at the cell surface even though it retains the putative RCK domains and down stream trafficking signals. Functionally, the hSlo Delta(579-664) variant acts as a dominant negative subunit to suppress cell surface expression of BK channels. Thus alternative splicing of the intracellular RCK1-RCK2 linker plays a critical role in determining cell surface expression of BK channels by controlling the inclusion/exclusion of multiple trafficking motifs.
- Subjects :
- BK channel
Potassium Channels
Amino Acid Motifs
Molecular Sequence Data
Intracellular Space
Biology
Biochemistry
Ion Channels
Cell Line
Cell membrane
03 medical and health sciences
Mice
0302 clinical medicine
Membrane Biology
medicine
Animals
Humans
Protein Isoforms
Amino Acid Sequence
Large-Conductance Calcium-Activated Potassium Channels
Cloning, Molecular
Molecular Biology
Ion channel
030304 developmental biology
Sequence Deletion
0303 health sciences
Trafficking
Endoplasmic reticulum
Alternative splicing
Cell Membrane
Biological Transport
Cell Biology
Exons
16. Peace & justice
Potassium channel
Calcium-activated potassium channel
Cell biology
Protein Structure, Tertiary
Alternative Splicing
medicine.anatomical_structure
Gene Expression Regulation
Membrane Trafficking
biology.protein
Cell Surface Protein
030217 neurology & neurosurgery
Intracellular
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Database :
- OpenAIRE
- Journal :
- The Journal of Biological Chemistry, Chen, L, Jeffries, O, Rowe, I C M, Liang, Z, Knaus, H G, Ruth, P & Shipston, M J 2010, ' Membrane Trafficking of Large Conductance Calcium-activated Potassium Channels Is Regulated by Alternative Splicing of a Transplantable, Acidic Trafficking Motif in the RCK1-RCK2 Linker ', Journal of Biological Chemistry, vol. 285, no. 30, pp. 23263-23273 . https://doi.org/10.1074/jbc.M110.139758
- Accession number :
- edsair.doi.dedup.....1aa9fe20e4292d72d138475cd3b9ac63