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• W1985884124 startingPage "e5896" @default.
• W1985884124 abstract "Non-covalent and covalent homo-oligomerization of membrane proteins regulates their subcellular localization and function. Here, we described a novel oligomerization mechanism affecting solute carrier family 30 member 3/zinc transporter 3 (SLC30A3/ZnT3). Oligomerization was mediated by intermolecular covalent dityrosine bonds. Using mutagenized ZnT3 expressed in PC12 cells, we identified two critical tyrosine residues necessary for dityrosine-mediated ZnT3 oligomerization. ZnT3 carrying the Y372F mutation prevented ZnT3 oligomerization, decreased ZnT3 targeting to synaptic-like microvesicles (SLMVs), and decreased resistance to zinc toxicity. Strikingly, ZnT3 harboring the Y357F mutation behaved as a gain-of-function mutant as it displayed increased ZnT3 oligomerization, targeting to SLMVs, and increased resistance to zinc toxicity. Single and double tyrosine ZnT3 mutants indicate that the predominant dimeric species is formed between tyrosine 357 and 372. ZnT3 tyrosine dimerization was detected under normal conditions and it was enhanced by oxidative stress. Covalent species were also detected in other SLC30A zinc transporters localized in different subcellular compartments. These results indicate that covalent tyrosine dimerization of a SLC30A family member modulates its subcellular localization and zinc transport capacity. We propose that dityrosine-dependent membrane protein oligomerization may regulate the function of diverse membrane protein in normal and disease states." @default.
• W1985884124 created "2016-06-24" @default.
• W1985884124 creator A5007378854 @default.
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• W1985884124 date "2009-06-12" @default.
• W1985884124 modified "2023-10-15" @default.
• W1985884124 title "SLC30A3 (ZnT3) Oligomerization by Dityrosine Bonds Regulates Its Subcellular Localization and Metal Transport Capacity" @default.
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• W1985884124 doi "https://doi.org/10.1371/journal.pone.0005896" @default.
• W1985884124 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2690824" @default.
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• W1985884124 hasPublicationYear "2009" @default.
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