| Impaired trafficking and intracellular retention of mutant kidney anion exchanger 1 proteins (G701D and A858D) associated with distal renal tubular acidosis. | |
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MedLine Citation:
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PMID: 20151848 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Novel compound heterozygous mutations, G701D, a recessive mutation, and A858D, a mild dominant mutation, of human solute carrier family 4, anion exchanger, member 1 (SLC4A1) were identified in two pediatric patients with distal renal tubular acidosis (dRTA). To examine the interaction, trafficking, and cellular localization of the wild-type and two mutant kidney AE1 (kAE1) proteins, we expressed the proteins alone or together in human embryonic kidney (HEK) 293T and Madin-Darby canine kidney (MDCK) epithelial cells. In individual expressions, wild-type kAE1 was localized at the cell surface of HEK 293T and the basolateral membrane of MDCK cells. In contrast, kAE1 G701D was mainly retained intracellularly, while kAE1 A858D was observed intracellularly and at the cell surface. In co-expression experiments, wild-type kAE1 formed heterodimers with kAE1 G701D and kAE1 A858D, and promoted the cell surface expression of the mutant proteins. The co-expressed kAE1 G701D and A858D could also form heterodimers but showed predominant intracellular retention in HEK 293T and MDCK cells. Thus impaired trafficking of the kAE1 G701D and A858D mutants would lead to a profound decrease in functional kAE1 at the basolateral membrane of alpha-intercalated cells in the distal nephron of the patients with dRTA. |
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Authors:
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Duangporn Ungsupravate; Nunghathai Sawasdee; Sookkasem Khositseth; Wandee Udomchaiprasertkul; Siri Khoprasert; Jing Li; Reinhart A F Reithmeier; Pa-Thai Yenchitsomanus |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular membrane biology Volume: 27 ISSN: 1464-5203 ISO Abbreviation: Mol. Membr. Biol. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-03-25 Completed Date: 2010-07-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9430797 Medline TA: Mol Membr Biol Country: England |
Other Details:
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Languages: eng Pagination: 92-103 Citation Subset: IM |
Affiliation:
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Division of Medical Molecular Biology, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acidosis, Renal Tubular
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metabolism* Amino Acid Substitution / genetics* Animals Anion Exchange Protein 1, Erythrocyte / metabolism* Blotting, Western Cell Extracts Cell Line Child Dogs Flow Cytometry Fluorescent Antibody Technique Humans Intracellular Space / metabolism* Mutant Proteins / metabolism* Protein Multimerization Protein Transport Subcellular Fractions / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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FRN15266//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Anion Exchange Protein 1, Erythrocyte; 0/Cell Extracts; 0/Mutant Proteins; 0/SLC4A1 protein, human |
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