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Quality Control and Substrate‐Dependent Downregulation of the Nutrient Transporter Fur4
Author(s) -
Keener Justin M.,
Babst Markus
Publication year - 2013
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/tra.12039
Subject(s) - degron , downregulation and upregulation , microbiology and biotechnology , transporter , biology , ubiquitin , chaperone (clinical) , biochemistry , ubiquitin ligase , gene , medicine , pathology
Upon exposure to stress conditions, unfolded cell‐surface nutrient transporters are rapidly internalized and degraded via the multivesicular body ( MVB ) pathway. Similarly, high concentrations of nutrients result in the downregulation of the corresponding transporters. Our studies using the yeast transporter Fur4 revealed that substrate‐induced downregulation and quality control utilize a common mechanism. This mechanism is based on a conformation‐sensing domain, termed LID (loop interaction domain), that regulates site‐specific ubiquitination (also known as degron). Conformational alterations in the transporter induced by unfolding or substrate binding are transmitted to the LID , rendering the degron accessible for ubiquitination by Rsp5. As a consequence, the transporter is rapidly degraded. We propose that the LID –degron system is a conserved, chaperone‐independent mechanism responsible for conformation‐induced downregulation of many cell‐surface transporters under physiological and pathological conditions.