2. Academic Validation
  3. Tetrameric Assembly of K+ Channels Requires ER-Located Chaperone Proteins

Tetrameric Assembly of K+ Channels Requires ER-Located Chaperone Proteins

  • Mol Cell. 2017 Jan 5;65(1):52-65. doi: 10.1016/j.molcel.2016.10.027.
Kai Li 1,  Qiang Jiang 1,  Xue Bai 1,  Yi-Feng Yang 2,  Mei-Yu Ruan 2,  Shi-Qing Cai 3
Affiliations

Affiliations

  • 1 Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Shanghai 200031, PRC.
  • 2 Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  • 3 Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: sqcai@ion.ac.cn.
PMID: 27916661 DOI: 10.1016/j.molcel.2016.10.027
Abstract

Tetrameric assembly of channel subunits in the endoplasmic reticulum (ER) is essential for surface expression and function of K+ channels, but the molecular mechanism underlying this process remains unclear. In this study, we found through genetic screening that ER-located J-domain-containing chaperone proteins (J-proteins) are critical for the biogenesis and physiological function of ether-a-go-go-related gene (ERG) K+ channels in both Caenorhabditis elegans and human cells. Human J-proteins DNAJB12 and DNAJB14 promoted tetrameric assembly of ERG (and Kv4.2) K+ channel subunits through a heat shock protein (HSP) 70-independent mechanism, whereas a mutated DNAJB12 that did not undergo oligomerization itself failed to assemble ERG channel subunits into tetramers in vitro and in C. elegans. Overexpressing DNAJB14 significantly rescued the defective function of human ether-a-go-go-related gene (hERG) mutant channels associated with long QT syndrome (LQTS), a condition that predisposes to life-threatening arrhythmia, by stabilizing the mutated proteins. Thus, chaperone proteins are required for subunit stability and assembly of K+ channels.

Keywords

C. elegans; J-protein; chaperone protein; hERG; long QT syndrome; potassium channel; protein biogenesis; protein oligomerization; protein trafficking; subunit assembly.

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