Impact of KCNE subunits on KCNQ1 (Kv7.1) channel membrane surface targeting
Article first published online: 7 JUN 2010
Copyright © 2010 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 225, Issue 3, pages 692–700, December 2010
How to Cite
Roura-Ferrer, M., Solé, L., Oliveras, A., Dahan, R., Bielanska, J., Villarroel, Á., Comes, N. and Felipe, A. (2010), Impact of KCNE subunits on KCNQ1 (Kv7.1) channel membrane surface targeting. J. Cell. Physiol., 225: 692–700. doi: 10.1002/jcp.22265
- Issue published online: 15 DEC 2010
- Article first published online: 7 JUN 2010
- Manuscript Accepted: 25 MAY 2010
- Manuscript Received: 13 JAN 2010
- Ministerio de Ciencia e Innovación (MICINN), Spain. Grant Numbers: BFU2008-00431, CSD2008-00005
The KCNQ1 (Kv7.1) channel plays an important role in cardiovascular physiology. Cardiomyocytes co-express KCNQ1 with KCNE1-5 proteins. KCNQ1 may co-associate with multiple KCNE regulatory subunits to generate different biophysically and pharmacologically distinct channels. Increasing evidence indicates that the location and targeting of channels are important determinants of their function. In this context, the presence of K+ channels in sphingolipid–cholesterol-enriched membrane microdomains (lipid rafts) is under investigation. Lipid rafts are important for cardiovascular functioning. We aimed to determine whether KCNE subunits modify the localization and targeting of KCNQ1 channels in lipid rafts microdomains. HEK-293 cells were transiently transfected with KCNQ1 and KCNE1–5, and their traffic and presence in lipid rafts were analyzed. Only KCNQ1 and KCNE3, when expressed alone, co-localized in raft fractions. In addition, while KCNE2 and KCNE5 notably stained the cell surface, KCNQ1 and the rest of the KCNEs showed strong intracellular retention. KCNQ1 targets multiple membrane surface microdomains upon association with KCNE peptides. Thus, while KCNQ1/KCNE1 and KCNQ1/KCNE2 channels target lipid rafts, KCNQ1 associated with KCNE3–5 did not. Channel membrane dynamics, analyzed by fluorescence recovery after photobleaching (FRAP) experiments, further supported these results. In conclusion, the trafficking and targeting pattern of KCNQ1 can be influenced by its association with KCNEs. Since KCNQ1 is crucial for cardiovascular physiology, the temporal and spatial regulations that different KCNE subunits may confer to the channels could have a dramatic impact on membrane electrical activity and putative endocrine regulation. J. Cell. Physiol. 225: 692–700, 2010. © 2010 Wiley-Liss, Inc.