A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels - PubMed (original) (raw)

A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels

N Zerangue et al. Neuron. 1999 Mar.

Free article

Abstract

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.

PubMed Disclaimer

Similar articles

• Identification and characterization of a novel member of the ATP-sensitive K+ channel subunit family, Kir6.3, in zebrafish.
  Zhang C, Miki T, Shibasaki T, Yokokura M, Saraya A, Seino S. Zhang C, et al. Physiol Genomics. 2006 Feb 14;24(3):290-7. doi: 10.1152/physiolgenomics.00228.2005. Epub 2005 Nov 29. Physiol Genomics. 2006. PMID: 16317080
• Defective trafficking and function of KATP channels caused by a sulfonylurea receptor 1 mutation associated with persistent hyperinsulinemic hypoglycemia of infancy.
  Cartier EA, Conti LR, Vandenberg CA, Shyng SL. Cartier EA, et al. Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2882-7. doi: 10.1073/pnas.051499698. Proc Natl Acad Sci U S A. 2001. PMID: 11226335 Free PMC article.
• Identification of a familial hyperinsulinism-causing mutation in the sulfonylurea receptor 1 that prevents normal trafficking and function of KATP channels.
  Taschenberger G, Mougey A, Shen S, Lester LB, LaFranchi S, Shyng SL. Taschenberger G, et al. J Biol Chem. 2002 May 10;277(19):17139-46. doi: 10.1074/jbc.M200363200. Epub 2002 Feb 26. J Biol Chem. 2002. PMID: 11867634
• Toward understanding the assembly and structure of KATP channels.
  Aguilar-Bryan L, Clement JP 4th, Gonzalez G, Kunjilwar K, Babenko A, Bryan J. Aguilar-Bryan L, et al. Physiol Rev. 1998 Jan;78(1):227-45. doi: 10.1152/physrev.1998.78.1.227. Physiol Rev. 1998. PMID: 9457174 Review.
• ATP-sensitive potassium channels: a model of heteromultimeric potassium channel/receptor assemblies.
  Seino S. Seino S. Annu Rev Physiol. 1999;61:337-62. doi: 10.1146/annurev.physiol.61.1.337. Annu Rev Physiol. 1999. PMID: 10099692 Review.

Cited by

• The puzzle of TRPV4 channelopathies.
  Nilius B, Voets T. Nilius B, et al. EMBO Rep. 2013 Feb;14(2):152-63. doi: 10.1038/embor.2012.219. Epub 2013 Jan 11. EMBO Rep. 2013. PMID: 23306656 Free PMC article. Review.
• The Conserved Arginine Cluster in the Insert of the Third Cytoplasmic Loop of the Long Form of the D₂ Dopamine Receptor (D2L-R) Acts as an Intracellular Retention Signal.
  Kubale V, Blagotinšek K, Nøhr J, Eidne KA, Vrecl M. Kubale V, et al. Int J Mol Sci. 2016 Jul 19;17(7):1152. doi: 10.3390/ijms17071152. Int J Mol Sci. 2016. PMID: 27447620 Free PMC article.
• Production and purification of ATP-sensitive potassium channel particles for cryo-electron microscopy.
  Driggers CM, Shyng SL. Driggers CM, et al. Methods Enzymol. 2021;653:121-150. doi: 10.1016/bs.mie.2021.02.008. Epub 2021 Mar 22. Methods Enzymol. 2021. PMID: 34099169 Free PMC article.
• 14-3-3ζ Protein regulates anterograde transport of the human κ-opioid receptor (hKOPR).
  Li JG, Chen C, Huang P, Wang Y, Liu-Chen LY. Li JG, et al. J Biol Chem. 2012 Nov 2;287(45):37778-92. doi: 10.1074/jbc.M112.359679. Epub 2012 Sep 18. J Biol Chem. 2012. PMID: 22989890 Free PMC article.
• Potential use of potassium efflux-deficient yeast for studying trafficking signals and potassium channel functions.
  Bernstein JD, Okamoto Y, Kim M, Shikano S. Bernstein JD, et al. FEBS Open Bio. 2013 Apr 16;3:196-203. doi: 10.1016/j.fob.2013.04.002. Print 2013. FEBS Open Bio. 2013. PMID: 23772394 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • Guide to Pharmacology