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| Subject Categories: Membranes & Transport | Proteins |
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| The EMBO Journal
(2006) 25, 5659–5669, doi:10.1038/sj.emboj.7601429 Published online 16 November 2006 |
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| The HECT ubiquitin ligase AIP4 regulates the cell surface expression of select TRP channels |
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| Tomasz Wegierski1, Kerstin Hill2, Michael Schaefer2 and Gerd Walz1 |
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1 Renal Division, University Hospital Freiburg, Freiburg, Germany 2 Department of Pharmacology, Charite—Campus Benjamin Franklin, Thielallee, Berlin, Germany To whom correspondence should be addressed Gerd Walz, Renal Division, University Hospital Freiburg, Hugstetter Strasse 55, Freiburg 79106, Germany. Tel.: +49 761 270 3250; Fax: +49 761 270 3245; E-mail: gerd.walz@uniklinik-freiburg.de Received 7 April 2006; Accepted 19 October 2006; Published online 16 November 2006. |
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| Abstract |
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| TRPV4 is a widely expressed member of the transient receptor potential (TRP) family that facilitates Ca2+ entry into nonexcitable cells. TRPV4 is activated by several stimuli, but it is largely unknown how the activity of this channel is terminated. Here, we show that ubiquitination represents an important mechanism to control the presence of TRPV4 at the plasma membrane. Ubiquitination of TRPV4 is dramatically increased by the HECT (homologous to E6-AP carboxyl terminus)-family ubiquitin ligase AIP4 without inducing degradation of this channel. Instead, AIP4 promotes the endocytosis of TRPV4 and decreases its amount at the plasma membrane. Consequently, the basal activity of TRPV4 is reduced despite an overall increase in TRPV4 levels. This mode of regulation is not limited to TRPV4. TRPC4, another member of the TRP channel family, is also strongly ubiquitinated in the presence of AIP4, leading to the increased intracellular localization of TRPC4 and the reduction of its basal activity. However, ubiquitination of several other TRP channels is not affected by AIP4, demonstrating that AIP4-mediated regulation is a unique property of select TRP channels. |
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| Keywords: endocytosis, transient receptor potential, TRPC4, TRPV4, ubiquitination |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHThe HECT ubiquitin ligase AIP4 regulates the cell surface expression of select TRP channels The EMBO Journal Article Regulation of stability and function of the epithelial Na + channel (ENaC) by ubiquitination The EMBO Journal Article (01 Nov 1997) Regulation of the epithelial Na + channel by Nedd4 and ubiquitination Kidney International Original Article CISK attenuates degradation of the chemokine receptor CXCR4 via the ubiquitin ligase AIP4 The EMBO Journal Article (23 Aug 2006) |
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