Trafficking defects in PAS domain mutant Kv11.1 channels: Roles of reduced domain stability and altered domain-domain interactions

Biochemical Journal

Volumn 454, Issue 1, 2013, Pages 69-77

  Ke, Ying ^a   Ng, Chai Ann ^a,b   Hunter, Mark J ^a   Mann, Stefan A ^a,b   Heide, Juliane ^a   Hill, Adam P ^a,b   Vandenberg, Jamie I ^a,b  

^a VICTOR CHANG CARDIAC RESEARCH INSTITUTE   (Australia)

^b UNIVERSITY OF NEW SOUTH WALES   (Australia)

Author keywords

Genotype phenotype relationship; Human ethera go go related gene; KCNH2; Long QT syndrome; Protein trafficking

Indexed keywords

POTASSIUM CHANNEL; POTASSIUM CHANNEL HERG; POTASSIUM CHANNEL KV11.1; UNCLASSIFIED DRUG;

ARTICLE; CELL MEMBRANE; CELL STRAIN HEK293; DNA SEQUENCE; FEMALE; GENOTYPE PHENOTYPE CORRELATION; HUMAN; HUMAN CELL; MISSENSE MUTATION; MUTANT; NONHUMAN; POLYACRYLAMIDE GEL ELECTROPHORESIS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN INTERACTION; PROTEIN STABILITY; REAL TIME POLYMERASE CHAIN REACTION; THERMOSTABILITY; WESTERN BLOTTING; XENOPUS LAEVIS;

ANIMALS; CHO CELLS; CRICETINAE; CRICETULUS; ETHER-A-GO-GO POTASSIUM CHANNELS; FEMALE; HEK293 CELLS; HUMANS; MUTATION; PROTEIN BINDING; PROTEIN TRANSPORT; PROTEIN-SERINE-THREONINE KINASES; XENOPUS LAEVIS;

EID: 84880865387     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20130328     Document Type: Article

References (32)

1. Curran, M. E., Splawski, I., Timothy, K. W., Vincent, G. M., Green, E. D. and Keating, M. T. (1995) A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 80, 795-803.
2. Knollmann, B. C. and Roden, D. M. (2008) A genetic framework for improving arrhythmia therapy. Nature 451, 929-936.
3. Kaltman, J. R., Thompson, P. D., Lantos, J., Berul, C. I., Botkin, J., Cohen, J. T., Cook, N. R., Corrado, D., Drezner, J., Frick, K. D. et al. (2011) Screening for sudden cardiac death in the young: report from a national heart, lung, and blood institute working group. Circulation 123, 1911-1918.
4. Deutsch, C. (2002) Potassium channel ontogeny. Annu. Rev. Physiol. 64, 19-46.
5. Morais Cabral, J. H., Lee, A., Cohen, S. L., Chait, B. T., Li, M. and Mackinnon, R. (1998) Crystal structure and functional analysis of the HERG potassium channel N terminus: A eukaryotic PAS domain. Cell 95, 649-655.
6. Warmke, J. W. and Ganetzky, B. (1994) A family of potassium channel genes related to eag in Drosophila and mammals. Proc. Natl. Acad. Sci. U.S.A. 91, 3438-3442.
7. Aydar, E. and Palmer, C. (2001) Functional characterization of the C-terminus of the human ether-A-go-go-related gene K+ channel (HERG). J. Physiol. 534, 1-14.
8. Akhavan, A., Atanasiu, R. and Shrier, A. (2003) Identification of a COOH-terminal segment involved in maturation and stability of human ether-A-go-go-related gene potassium channels. J. Biol. Chem. 278, 40105-40112.
9. Jones, E. M., Roti Roti, E. C., Wang, J., Delfosse, S. A. and Robertson, G. A. (2004) Cardiac IKr channels minimally comprise hERG 1a and 1b subunits. J. Biol. Chem. 279, 44690-44694.
10. Phartiyal, P., Jones, E. M. and Robertson, G. A. (2007) Heteromeric assembly of human ether-A-go-go-related gene (hERG) 1a/1b channels occurs cotranslationally via N-terminal interactions. J. Biol. Chem. 282, 9874-9882.
11. Anderson, C. L., Delisle, B. P., Anson, B. D., Kilby, J. A., Will, M. L., Tester, D. J., Gong, Q., Zhou, Z., Ackerman, M. J. and January, C. T. (2006) Most LQT2 mutations reduce Kv11.1 (hERG) current by a class 2 (trafficking-deficient) mechanism. Circulation 113, 365-373.
12. Walker, V. E., Atanasiu, R., Lam, H. and Shrier, A. (2007) Co-chaperone FKBP38 promotes HERG trafficking. J. Biol. Chem. 282, 23509-23516.
13. Walker, V. E., Wong, M. J., Atanasiu, R., Hantouche, C., Young, J. C. and Shrier, A. (2010) Hsp40 chaperones promote degradation of the HERG potassium channel. J. Biol. Chem. 285, 3319-3329.
14. Ellgaard, L. and Helenius, A. (2003) Quality control in the endoplasmic reticulum. Nat. Rev. Mol. Cell Biol. 4, 181-191.
15. Li, Q., Gayen, S., Chen, A. S., Huang, Q., Raida, M. and Kang, C. (2010) NMR solution structure of the N-terminal domain of hERG and its interaction with the S4-S5 linker. Biochem. Biophys. Res. Commun. 403, 126-132.
16. Muskett, F. W., Thouta, S., Thomson, S. J., Bowen, A., Stansfeld, P. J. and Mitcheson, J. S. (2011) Mechanistic insight into human ether-A-go-go-related gene (hERG) K+ channel deactivation gating from the solution structure of the EAG domain. J. Biol. Chem. 286, 6184-6191.
17. Ng, C. A., Hunter, M. J., Perry, M. D., Mobli, M., Ke, Y., Kuchel, P. W., King, G. F., Stock, D. and Vandenberg, J. I. (2011) The N-terminal tail of hERG contains an amphipathic α-helix that regulates channel deactivation. PLoS ONE 6, e16191.
18. Gustina, A. S. and Trudeau, M. C. (2011) hERG potassium channel gating is mediated by N- And C-terminal region interactions. J. Gen. Physiol. 137, 315-325.
19. Gustina, A. S. and Trudeau, M. C. (2009) A recombinant N-terminal domain fully restores deactivation gating in N-truncated and long QT syndrome mutant hERG potassium channels. Proc. Natl. Acad. Sci. U.S.A. 106, 13082-13087.
20. Vandenberg, J. I., Perry, M. D., Perrin, M. J., Mann, S. A., Ke, Y. and Hill, A. P. (2012) hERG K+ channels: structure, function, and clinical significance. Physiol. Rev. 92, 1393-1478.
21. Zhao, J. T., Hill, A. P., Varghese, A., Cooper, A. A., Swan, H., Laitinen-Forsblom, P. J., Rees, M. I., Skinner, J. R., Campbell, T. J. and Vandenberg, J. I. (2009) Not all hERG pore domain mutations have a severe phenotype: G584S has an inactivation gating defect with mild phenotype compared to G572S, which has a dominant negative trafficking defect and a severe phenotype. J. Cardiovasc. Electrophysiol. 20, 923-930.
22. Wang, J., Trudeau, M. C., Zappia, A. M. and Robertson, G. A. (1998) Regulation of deactivation by an amino terminal domain in human ether-A-go-go-related gene potassium channels. J. Gen. Physiol. 112, 637-647.
23. Rajamani, S., Anderson, C. L., Valdivia, C. R., Eckhardt, L. L., Foell, J. D., Robertson, G. A., Kamp, T. J., Makielski, J. C., Anson, B. D. and January, C. T. (2006) Specific serine proteases selectively damage KCNH2 (hERG1) potassium channels and IKr. Am. J. Physiol. Heart. Circ. Physiol. 290, H1278-H1288.
24. Guo, J., Massaeli, H., Li, W., Xu, J., Luo, T., Shaw, J., Kirshenbaum, L. A. and Zhang, S. (2007) Identification of IKr and its trafficking disruption induced by probucol in cultured neonatal rat cardiomyocytes. J. Pharmacol. Exp. Ther. 321, 911-920.
25. Berecki, G., Zegers, J. G., Verkerk, A. O., Bhuiyan, Z. A., de Jonge, B., Veldkamp, M. W., Wilders, R. and van Ginneken, A. C. (2005) HERG channel (dys)function revealed by dynamic action potential clamp technique. Biophys. J. 88, 566-578.
26. Zhou, Z., Gong, Q. and January, C. T. (1999) Correction of defective protein trafficking of a mutant HERG potassium channel in human long QT syndrome. Pharmacological and temperature effects. J. Biol. Chem. 274, 31123-31126.
27. Harley, C. A., Jesus, C. S., Carvalho, R., Brito, R. M. and Morais-Cabral, J. H. (2012) Changes in channel trafficking and protein stability caused by LQT2 mutations in the PAS domain of the HERG channel. PLoS ONE 7, e32654.
28. Gustina, A. S. and Trudeau, M. C. (2013) The eag domain regulates hERG channel inactivation gating via a direct interaction. J. Gen. Physiol. 141, 229-241.
29. Erbel, P. J., Card, P. B., Karakuzu, O., Bruick, R. K. and Gardner, K. H. (2003) Structural basis for PAS domain heterodimerization in the basic helix-loop-helix-PAS transcription factor hypoxia-inducible factor. Proc. Natl. Acad. Sci. U.S.A. 100, 15504-15509.
30. Gianulis, E. C. and Trudeau, M. C. (2011) Rescue of aberrant gating by a geneticallyencoded PAS (Per-Arnt-Sim) domain in several long QT syndrome mutant human ERG (hERG) potassium channels. J. Biol. Chem. 286, 22160-22169.
31. Kim, J. A., Lopes, C. M., Moss, A. J., McNitt, S., Barsheshet, A., Robinson, J. L., Zareba, W., Ackerman, M. J., Kaufman, E. S., Towbin, J. A. et al. (2010) Trigger-specific risk factors and response to therapy in long QT syndrome type 2. Heart Rhythm. 7, 1797-1805.
32. Shimizu, W., Moss, A. J., Wilde, A. A., Towbin, J. A., Ackerman, M. J., January, C. T., Tester, D. J., Zareba, W., Robinson, J. L., Qi, M. et al. (2009) Genotype-phenotype aspects of type 2 long QT syndrome. J. Am. Coll. Cardiol. 54, 2052-2062.