HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, X. Articles by Li, M. Search for Related Content PubMed PubMed Citation Articles by Li, X. Articles by Li, M. Social Bookmarking                      What's this?

Volume 272, Number 2, Issue of January 10, 1997 pp. 705-708
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

---

COMMUNICATION:
The Human 1261 Mutation of the HERG Potassium Channel Results in a Truncated Protein That Contains a Subunit Interaction Domain and Decreases the Channel Expression

(Received for publication, June 24, 1996, and in revised form, October 1, 1996)

Xiaodong Li , Jia Xu and Min Li

From the Department of Physiology and  Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

HERG (uman -elated ene) encodes an inward-rectifier potassium channel formed by the assembly of four subunits. Since the truncated HERG protein in patients with long QT syndrome induces a dominant phenotype, that is, cardiac sudden death, the assembly of nonfunctional complexes between wild-type and mutated subunits was implicated in causing the disease. To understand HERG-mediated cardiac sudden death at the molecular level, it is important to determine which regions in the HERG protein participate in subunit interaction. We therefore report the identification of a subunit interaction domain, NAB_HERG, that is localized at the hydrophilic cytoplasmic N terminus and can form a tetramer in the absence of the rest of the HERG protein. Truncated HERG proteins containing NAB_HERG, including one that resulted from the 1261 human mutation, inhibit the functional expression of the HERG channel in transfected cells. Together, these results support the notion that the expression of HERG in the human heart may be decreased in the presence of the truncated subunit. Such a decrease of potassium channel expression can contribute to the longer QT intervals observed in the patients with the HERG mutation.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Q. Gong, L. Zhang, G. M. Vincent, B. D. Horne, and Z. Zhou Nonsense Mutations in hERG Cause a Decrease in Mutant mRNA Transcripts by Nonsense-Mediated mRNA Decay in Human Long-QT Syndrome Circulation, July 3, 2007; 116(1): 17 - 24. [Abstract] [Full Text] [PDF]

				P. Phartiyal, E. M. C. Jones, and G. A. Robertson Heteromeric Assembly of Human Ether-a-go-go-related Gene (hERG) 1a/1b Channels Occurs Cotranslationally via N-terminal Interactions J. Biol. Chem., March 30, 2007; 282(13): 9874 - 9882. [Abstract] [Full Text] [PDF]

				A. D.C. Paulussen, A. Raes, R. J. Jongbloed, R. A.H.J. Gilissen, A. A.M. Wilde, D. J. Snyders, H. J.M. Smeets, and J. Aerssens HERG mutation predicts short QT based on channel kinetics but causes long QT by heterotetrameric trafficking deficiency Cardiovasc Res, August 15, 2005; 67(3): 467 - 475. [Abstract] [Full Text] [PDF]

				I. Cherel Regulation of K+ channel activities in plants: from physiological to molecular aspects J. Exp. Bot., February 1, 2004; 55(396): 337 - 351. [Abstract] [Full Text] [PDF]

				F.-D. Huang, J. Chen, M. Lin, M. T. Keating, and M. C. Sanguinetti Long-QT Syndrome-Associated Missense Mutations in the Pore Helix of the HERG Potassium Channel Circulation, August 28, 2001; 104(9): 1071 - 1075. [Abstract] [Full Text] [PDF]

				C. E. Clancy and Y. Rudy Cellular consequences of HERG mutations in the long QT syndrome: precursors to sudden cardiac death Cardiovasc Res, May 1, 2001; 50(2): 301 - 313. [Abstract] [Full Text] [PDF]

				C.-C. Shieh, M. Coghlan, J. P. Sullivan, and M. Gopalakrishnan Potassium Channels: Molecular Defects, Diseases, and Therapeutic Opportunities Pharmacol. Rev., December 1, 2000; 52(4): 557 - 594. [Abstract] [Full Text] [PDF]

				C.-E. Chiang and D. M. Roden The long QT syndromes: genetic basis and clinical implications J. Am. Coll. Cardiol., July 1, 2000; 36(1): 1 - 12. [Abstract] [Full Text] [PDF]

				A. Jeron, G. F. Mitchell, J. Zhou, M. Murata, B. London, P. Buckett, S. D. Wiviott, and G. Koren Inducible polymorphic ventricular tachyarrhythmias in a transgenic mouse model with a long Q-T phenotype Am J Physiol Heart Circ Physiol, June 1, 2000; 278(6): H1891 - H1898. [Abstract] [Full Text] [PDF]

				A. Kagan, Z. Yu, G. I. Fishman, and T. V. McDonald The Dominant Negative LQT2 Mutation A561V Reduces Wild-type HERG Expression J. Biol. Chem., April 6, 2000; 275(15): 11241 - 11248. [Abstract] [Full Text] [PDF]

				D. M Roden and J. R Balser A plethora of mechanisms in the HERG-related long QT syndrome: Genetics meets electrophysiology Cardiovasc Res, November 1, 1999; 44(2): 242 - 246. [Full Text] [PDF]

				T. Nakajima, T. Furukawa, Y. Hirano, T. Tanaka, H. Sakurada, T. Takahashi, R. Nagai, T. Itoh, Y. Katayama, Y. Nakamura, et al. Voltage-shift of the current activation in HERG S4 mutation (R534C) in LQT2 Cardiovasc Res, November 1, 1999; 44(2): 283 - 293. [Abstract] [Full Text] [PDF]

				F. Lehmann-Horn and K. Jurkat-Rott Voltage-Gated Ion Channels and Hereditary Disease Physiol Rev, October 1, 1999; 79(4): 1317 - 1372. [Abstract] [Full Text] [PDF]

				B. L. Taylor and I. B. Zhulin PAS Domains: Internal Sensors of Oxygen, Redox Potential, and Light Microbiol. Mol. Biol. Rev., June 1, 1999; 63(2): 479 - 506. [Abstract] [Full Text] [PDF]

				M. Furutani, M. C. Trudeau, N. Hagiwara, A. Seki, Q. Gong, Z. Zhou, S.-i. Imamura, H. Nagashima, H. Kasanuki, A. Takao, et al. Novel Mechanism Associated With an Inherited Cardiac Arrhythmia : Defective Protein Trafficking by the Mutant HERG (G601S) Potassium Channel Circulation, May 4, 1999; 99(17): 2290 - 2294. [Abstract] [Full Text] [PDF]

				J. Chen, A. Zou, I. Splawski, M. T. Keating, and M. C. Sanguinetti Long QT Syndrome-associated Mutations in the Per-Arnt-Sim (PAS) Domain of HERG Potassium Channels Accelerate Channel Deactivation J. Biol. Chem., April 9, 1999; 274(15): 10113 - 10118. [Abstract] [Full Text] [PDF]

				S. Kupershmidt, D. J. Snyders, A. Raes, and D. M. Roden A K+ Channel Splice Variant Common in Human Heart Lacks a C-terminal Domain Required for Expression of Rapidly Activating Delayed Rectifier Current J. Biol. Chem., October 16, 1998; 273(42): 27231 - 27235. [Abstract] [Full Text] [PDF]

				P. Babij, G. R. Askew, B. Nieuwenhuijsen, C.-M. Su, T. R. Bridal, B. Jow, T. M. Argentieri, J. Kulik, L. J. DeGennaro, W. Spinelli, et al. Inhibition of Cardiac Delayed Rectifier K+ Current by Overexpression of the Long-QT Syndrome HERG G628S Mutation in Transgenic Mice Circ. Res., September 21, 1998; 83(6): 668 - 678. [Abstract] [Full Text] [PDF]

				T. Nakajima, T. Furukawa, T. Tanaka, Y. Katayama, R. Nagai, Y. Nakamura, and M. Hiraoka Novel Mechanism of HERG Current Suppression in LQT2 : Shift in Voltage Dependence of HERG Inactivation Circ. Res., August 24, 1998; 83(4): 415 - 422. [Abstract] [Full Text] [PDF]

				S. H. Soderling, S. J. Bayuga, and J. A. Beavo Cloning and characterization of a cAMP-specific cyclic nucleotide phosphodiesterase PNAS, July 21, 1998; 95(15): 8991 - 8996. [Abstract] [Full Text] [PDF]

				B. London, A. Jeron, J. Zhou, P. Buckett, X. Han, G. F. Mitchell, and G. Koren Long QT and ventricular arrhythmias in transgenic mice expressing the N terminus and first transmembrane segment of a voltage-gated potassium channel PNAS, March 17, 1998; 95(6): 2926 - 2931. [Abstract] [Full Text] [PDF]

				E. Huala, P. W. Oeller, E. Liscum, I. Han, E. Larsen, and W. R. Briggs Arabidopsis NPH1: A Protein Kinase with a Putative Redox-Sensing Domain Science, December 19, 1997; 278(5346): 2120 - 2123. [Abstract] [Full Text]

				B. London, M. C. Trudeau, K. P. Newton, A. K. Beyer, N. G. Copeland, D. J. Gilbert, N. A. J enkins, C. A. Satler, and G. A. Robertson Two Isoforms of the Mouse Ether-a-go-go–Related Gene Coassemble to Form Channels With Properties Similar to the Rapidly Activating Component of the Cardiac Delayed Rectifier K+ Current Circ. Res., November 19, 1997; 81(5): 870 - 878. [Abstract] [Full Text]

				E. Folco, R. Mathur, Y. Mori, P. Buckett, and G. Koren A Cellular Model for Long QT Syndrome. TRAPPING OF HETEROMULTIMERIC COMPLEXES CONSISTING OF TRUNCATED Kv1.1 POTASSIUM CHANNEL POLYPEPTIDES AND NATIVE Kv1.4 AND Kv1.5 CHANNELS IN THE ENDOPLASMIC RETICULUM J. Biol. Chem., October 17, 1997; 272(42): 26505 - 26510. [Abstract] [Full Text] [PDF]

				J. Xu and M. Li Kvbeta 2 Inhibits the Kvbeta 1-mediated Inactivation of K+ Channels in Transfected Mammalian Cells J. Biol. Chem., May 2, 1997; 272(18): 11728 - 11735. [Abstract] [Full Text] [PDF]

				T.-H. Ngo, M. F. Hoylaerts, I. Knockaert, E. Brouwers, and P. J. Declerck Identification of a Target Site in Plasminogen Activator Inhibitor-1 That Allows Neutralization of Its Inhibitory Properties Concomitant with an Allosteric Up-regulation of Its Antiadhesive Properties J. Biol. Chem., July 6, 2001; 276(28): 26243 - 26248. [Abstract] [Full Text] [PDF]