A New ER Trafficking Signal Regulates the Subunit Stoichiometry of Plasma Membrane KATP Channels
Open accessAbstract
Proper ion channel function often requires specific combinations of pore-forming alpha and regulatory beta subunits, but little is known about the mechanisms that regulate the surface expression of different channel combinations. Our studies of ATP-sensitive K+ channel (K(ATP)) trafficking reveal an essential quality control function for a trafficking motif present in each of the alpha (Kir6.1/2) and beta (SUR1) subunits of the K(ATP) complex. We show that this novel motif for endoplasmic reticulum (ER) retention/retrieval is required at multiple stages of K(ATP) assembly to restrict surface expression to fully assembled and correctly regulated octameric channels. We conclude that exposure of a three amino acid motif (RKR) can explain how assembly of an ion channel complex is coupled to intracellular trafficking.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Both Kir6.2 and SUR1 subunits are required for correct trafficking of the KATP channel to the plasma membrane.
“Both subunits are also required for correct trafficking of the channel to the plasma membrane (757).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [757]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Association and Stoichiometry of KATP Channel Subunits
Clement, J. P., Kunjilwar, K., Gonzalez, G., Schwanstecher, M., Panten, U., Aguilar-Bryan, L., & Bryan, J. (1997) · Neuron · doi:10.1016/s0896-6273(00)80321-9 · Cited by 692 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- [1]1. Ashcroft, S.J ∙ Ashcroft, F.M Properties and functions of ATP-sensitive K-channels Cell. Signal. 1990; 2:197-214 Crossref Scopus (696) PubMed Google Scholar
- [2]2. Ausubel, F.M., Brent, R., Kingston, R.E., Moore, D.D., Seidman, J.G., Smith, J.A., and Struhl, K. (1997). Current Protocols in Molecular Biology. (New York: J. Wiley & Sons). Google Scholar
- [3]3. Babenko, A.P ∙ Aguilar-Bryan, L ∙ Bryan, J A view of sur/KIR6.X, KATP channels Annu. Rev. Physiol. 1998; 60:667-687 Crossref Scopus (494) PubMed Google Scholar
- [4]4. Blount, P ∙ Smith, M.M ∙ Merlie, J.P Assembly intermediates of the mouse muscle nicotinic acetylcholine receptor in stably transfected fibroblasts J. Cell Biol. 1990; 111:2601-2611 Crossref Scopus (77) PubMed Google Scholar
- [5]5. Bonifacino, J.S ∙ Cosson, P ∙ Klausner, R.D Colocalized transmembrane determinants for ER degradation and subunit assembly explain the intracellular fate of TCR chains Cell. 1990; 63:503-513
Cited by
Sorted by citations
Crucial Step in Cholesterol Homeostasis
Yang, T., Espenshade, P. J., Wright, M. E., Yabe, D., Gong, Y., Aebersold, R., Goldstein, J. L., & Brown, M. S. (2002) · Cell · doi:10.1016/s0092-8674(02)00872-3 · Cited by 987 · see citing works
Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
Rorsman, P., & Ashcroft, F. M. (2018) · Physiological Reviews · doi:10.1152/physrev.00008.2017 · Cited by 793 · see citing works
Subunit-Specific NMDA Receptor Trafficking to Synapses
Barria, A., & Malinow, R. (2002) · Neuron · doi:10.1016/s0896-6273(02)00776-6 · Cited by 515 · see citing works
Stargazin modulates AMPA receptor gating and trafficking by distinct domains
Tomita, S., Adesnik, H., Sekiguchi, M., Zhang, W., Wada, K., Howe, J. R., Nicoll, R. A., & Bredt, D. S. (2005) · Nature · doi:10.1038/nature03624 · Cited by 486 · see citing works
Alternative 3′ UTRs act as scaffolds to regulate membrane protein localization
Berkovits, B. D., & Mayr, C. (2015) · Nature · doi:10.1038/nature14321 · Cited by 474 · see citing works
An NMDA receptor ER retention signal regulated by phosphorylation and alternative splicing
Scott, D. B., Blanpied, T. A., Swanson, G. T., Zhang, C., & Ehlers, M. D. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-09-03063.2001 · Cited by 418 · see citing works
Mitochondrial potassium transport: the K+ cycle
Garlid, K. D., & Paucek, P. (2003) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(03)00108-7 · Cited by 365 · see citing works
Structure of a Pancreatic ATP-Sensitive Potassium Channel
Li, N., Wu, J.-X., Ding, D., Cheng, J., Gao, N., & Chen, L. (2017) · Cell · doi:10.1016/j.cell.2016.12.028 · Cited by 252 · see citing works
Yang, S.-B., Tien, A.-C., Boddupalli, G., Xu, A. W., Jan, Y. N., & Jan, L. Y. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.043 · Cited by 242 · see citing works
Self-citationLevitan, I., Fang, Y., Rosenhouse-Dantsker, A., & Romanenko, V. (2010) · Subcellular Biochemistry · doi:10.1007/978-90-481-8622-8_19 · Cited by 247 · see citing works
Michelsen, K., Yuan, H., & Schwappach, B. (2005) · The EMBO Reports · doi:10.1038/sj.embor.7400480 · Cited by 235 · see citing works
Self-citationNashmi, R., Dickinson, M. E., McKinney, S., Jareb, M., Labarca, C., Fraser, S. E., & Lester, H. A. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-37-11554.2003 · Cited by 188 · see citing works
Scott, D. B., Blanpied, T. A., & Ehlers, M. D. (2003) · Neuropharmacology · doi:10.1016/s0028-3908(03)00250-8 · Cited by 186 · see citing works
Matsuda, K., Fletcher, M., Kamiya, Y., & Yuzaki, M. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-31-10064.2003 · Cited by 138 · see citing works
Sulfonylurea and K+-Channel Opener Sensitivity of KATP Channels
Koster, J. C., Sha, Q., & Nichols, C. G. (1999) · The Journal of General Physiology · doi:10.1085/jgp.114.2.203 · Cited by 97 · see citing works
“2 results in the generation of ATP-sensitive channels in the absence of SURx subunits (Tucker et al., 1997; Zerangue et al., 1999), but these channels are not activated by MgADP or potassium channel openers (PCOs), nor are they inhibited at high affinity by sulfonylurea drugs, consistent with these…”
Polarized targeting of neurexins to synapses is regulated by their C-terminal sequences
Fairless, R., Masius, H., Rohlmann, A., Heupel, K., Ahmad, M., Reissner, C., Dresbach, T., & Missler, M. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.5294-07.2008 · Cited by 91 · see citing works
Brock, C., Boudier, L., Maurel, D., Blahos, J., & Pin, J.-P. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-05-0400 · Cited by 81 · see citing works
Babenko, A. P., Gonzalez, G., & Bryan, J. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01215-6 · Cited by 63 · see citing works
Gassmann, M., Haller, C., Stoll, Y., Aziz, S. A., Biermann, B., Mosbacher, J., Kaupmann, K., & Bettler, B. (2005) · Molecular Pharmacology · doi:10.1124/mol.104.010256 · Cited by 56 · see citing works
Kir6.2 mutations causing neonatal diabetes prevent endocytosis of ATP-sensitive potassium channels
Mankouri, J., Taneja, T. K., Smith, A. J., Ponnambalam, S., & Sivaprasadarao, A. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601275 · Cited by 51 · see citing works
- Authors
- Zerangue, N., Schwappach, B., Jan, Y. N., & Jan, L. Y.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Jan, Lily Yeh
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1999-03
- Volume
- 22
- Issue
- 3
- Pages
- 537-548
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2150796852
- Cited by
- 1,025
- References
- 1
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 9 · 2023: 11 · 2022: 18 · 2021: 18 · 2020: 11 · 2019: 18 · 2018: 18 · 2017: 24 · 2016: 25 · 2015: 29 · 2014: 29 · 2013: 35 · 2012: 44
- FWCI
- 19.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- GRO (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Neuron
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- Kir6.1, Kir6.2, SUR1, endoplasmic reticulum retention, subunit stoichiometry, ion channel assembly, quality control, cell surface expression, protein trafficking
- MeSH terms
- Adenosine Triphosphate, Amino Acid Sequence, Animals, Cell Membrane, Electrophysiology, Endoplasmic Reticulum, Flow Cytometry, Membrane Potentials, Molecular Sequence Data, Oocytes, Receptors, Drug, Xenopus, Potassium Channels, Signal Transduction, Patch-Clamp Techniques, ATP-Binding Cassette Transporters, Fluorescent Antibody Technique, Direct, COS Cells, Potassium Channels, Inwardly Rectifying, Mice, Rats, Sulfonylurea Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
