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| Subject Categories: Membranes & Transport | Proteins |
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| The EMBO Journal
(2006) 25, 662–672, doi:10.1038/sj.emboj.7600984 Published online 2 February 2006 |
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| Transferrin receptor-like proteins control the degradation of a yeast metal transporter |
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| Helen E M Stimpson, Michael J Lewis and Hugh R B Pelham |
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MRC Laboratory of Molecular Biology, Cambridge, UK To whom correspondence should be addressed Hugh R B Pelham, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK. Tel.: +44 1223 402290; Fax: +44 1223 412142; E-mail: hp@mrc-lmb.cam.ac.uk Received 24 May 2005; Accepted 11 January 2006; Published online 2 February 2006. |
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| Abstract |
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| Plasma membrane transporters are often downregulated by their substrates. The yeast manganese transporter Smf1 is subject to two levels of regulation: heavy metals induce its sequestration within the cell, and also its ubiquitination and degradation in the vacuole. Degradation requires Bsd2, a membrane protein with a PPxY motif that recruits the ubiquitin ligase Rsp5, and which has a role in the quality control of membrane proteins, that expose hydrophilic residues to the lipid bilayer. We show that degradation of Smf1 requires in addition one of a pair of related yeast proteins, Tre1 and Tre2, that also contain PPxY motifs. Tre1 can partially inhibit manganese uptake without Bsd2, but requires Bsd2 to induce Smf1 degradation. It has a relatively hydrophilic transmembrane domain and binds to Bsd2. We propose that the Tre proteins specifically link Smf1 to the Bsd2-dependent quality control system. Their luminal domains are related to the transferrin receptor, but these are dispensable for Smf1 regulation. Tre proteins and the transferrin receptors appear to have evolved independently from the same family of membrane-associated proteases. |
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| Keywords: Bsd2, metal transport, Rsp5, Smf1, ubiquitin |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHBsd2 binds the ubiquitin ligase Rsp5 and mediates the ubiquitination of transmembrane proteins The EMBO Journal Article (24 Mar 2004) A transmembrane ubiquitin ligase required to sort membrane proteins into multivesicular bodies Nature Cell Biology Article (01 Feb 2002) Sorting of proteins into multivesicular bodies: ubiquitin-dependent and -independent targeting The EMBO Journal Article (17 Sep 2001) Ubiquitin Lys63 is involved in ubiquitination of a yeast plasma membrane protein The EMBO Journal Article (01 Oct 1997) |
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