ArticlePloS one2009
SLC30A3 (ZnT3) oligomerization by dityrosine bonds regulates its subcellular localization and metal transport capacity.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 57 citations in OpenAlex.
- A dominant negative heterozygous G87R mutation in the zinc transporter, ZnT-2 (SLC30A2), results in transient neonatal zinc deficiency.The Journal of biological chemistry · 2012Trial
- The Astrocytic Zinc Transporter ZIP12 Is a Synaptic Protein That Contributes to Synaptic Zinc Levels in the Mouse Auditory Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Cochlear zinc signaling dysregulation is associated with noise-induced hearing loss, and zinc chelation enhances cochlear recovery.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Expression and Distribution of Free Zinc in Penile Erectile Tissue.The world journal of men's health · 2023Article
- Transmembrane 163 (TMEM163) protein interacts with specific mammalian SLC30 zinc efflux transporter family members.Biochemistry and biophysics reports · 2022Article
- Metal transport mechanism of the cation diffusion facilitator (CDF) protein family - a structural perspective on human CDF (ZnT)-related diseases.RSC chemical biology · 2021Review
- The Function and Regulation of Zinc in the Brain.Neuroscience · 2021Review
- Insights Into the Mechanism of MCT8 Oligomerization.Journal of the Endocrine Society · 2020Article
- Transcription factors and transporters in zinc homeostasis: lessons learned from fungi.Critical reviews in biochemistry and molecular biology · 2020Review
- Transmembrane 163 (TMEM163) protein effluxes zinc.Archives of biochemistry and biophysics · 2019Article
- The role of zinc and its compounds in leukemia.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Review
- The C-terminal cytosolic domain of the human zinc transporter ZnT8 and its diabetes risk variant.The FEBS journal · 2018Article
- Physiological roles of zinc transporters: molecular and genetic importance in zinc homeostasis.The journal of physiological sciences : JPS · 2017Review
- Loss of synaptic Zn2+ transporter function increases risk of febrile seizures.Scientific reports · 2015Article
- Membrane transporters in self resistance of Cercospora nicotianae to the photoactivated toxin cercosporin.Current genetics · 2015Article
- Heterodimerization, altered subcellular localization, and function of multiple zinc transporters in viable cells using bimolecular fluorescence complementation.The Journal of biological chemistry · 2015Article
- ZnT2 is a critical mediator of lysosomal-mediated cell death during early mammary gland involution.Scientific reports · 2015Article
- In situ dimerization of multiple wild type and mutant zinc transporters in live cells using bimolecular fluorescence complementation.The Journal of biological chemistry · 2014Article
- The Concise Guide to PHARMACOLOGY 2013/14: transporters.British journal of pharmacology · 2013Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
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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.
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