Source:http://linkedlifedata.com/resource/pubmed/id/17645432
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
2007-9-12
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pubmed:abstractText |
The Saccharomyces cerevisiae high-affinity copper transporter, Ctr1p, mediates cellular uptake of Cu(I). We report that when copper (50 microm CuSO(4)) is added to the growth medium of copper-starved cells, Ctr1p is rapidly internalized by endocytosis, delivered to the lumen of the lysosome-like vacuole and slowly degraded by vacuolar proteases. Through analysis of the trafficking and degradation of Ctr1p mutants, two lysine residues in the C-terminal cytoplasmic tail of Ctr1p, Lys340 and Lys345, were found to be critical for copper-dependent endocytosis and degradation. In response to copper addition, Ctr1p was found to be ubiquitylated and a mutation in the Rsp5 ubiquitin ligase largely abolished ubiquitylation, endocytosis and degradation. In a strain lacking the Rsp5p accessory factors Bul1p and Bul2p, endocytosis and degradation of Ctr1p-green fluorescent protein were substantially diminished. Surprisingly, a Ctr1p mutant that lacks Lys340 and Lys345 was still ubiquitylated in a copper-dependent manner, indicating that ubiquitylation of Ctr1p on other sites is insufficient to drive copper-dependent endocytosis and degradation. This study demonstrates that copper regulates turnover of Ctr1p by stimulating Rsp5p-dependent endocytosis and degradation of Ctr1p in the vacuole.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CTR1 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Cation Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Copper,
http://linkedlifedata.com/resource/pubmed/chemical/Endosomal Sorting Complexes...,
http://linkedlifedata.com/resource/pubmed/chemical/RSP5 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligase Complexes
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1398-9219
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1375-84
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17645432-Cation Transport Proteins,
pubmed-meshheading:17645432-Copper,
pubmed-meshheading:17645432-Endocytosis,
pubmed-meshheading:17645432-Endosomal Sorting Complexes Required for Transport,
pubmed-meshheading:17645432-Protein Transport,
pubmed-meshheading:17645432-Saccharomyces cerevisiae,
pubmed-meshheading:17645432-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:17645432-Ubiquitin-Protein Ligase Complexes,
pubmed-meshheading:17645432-Vacuoles
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pubmed:year |
2007
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pubmed:articleTitle |
Regulation of copper-dependent endocytosis and vacuolar degradation of the yeast copper transporter, Ctr1p, by the Rsp5 ubiquitin ligase.
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pubmed:affiliation |
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6058, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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