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Orai channels are c...
Orai channels are critical for receptor-mediated endocytosis of albumin
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- Zeng, Bo (author)
- Southwest Medical University,University of Hull
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- Chen, Gui Lan (author)
- Southwest Medical University,University of Hull
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- Garcia-Vaz, Eliana (author)
- Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups
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- Bhandari, Sunil (author)
- Hull Royal Infirmary
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- Daskoulidou, Nikoleta (author)
- University of Hull
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- Berglund, Lisa M. (author)
- Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups
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- Jiang, Hongni (author)
- University of Hull
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- Hallett, Thomas (author)
- University of Hull
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- Zhou, Lu Ping (author)
- Southwest Medical University
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- Huang, Li (author)
- Southwest Medical University
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- Xu, Zi Hao (author)
- Southwest Medical University
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- Nair, Viji (author)
- University of Michigan
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- Nelson, Robert G. (author)
- National Institute of Diabetes and Digestive and Kidney Diseases
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- Ju, Wenjun (author)
- University of Michigan
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- Kretzler, Matthias (author)
- University of Michigan
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- Atkin, Stephen L. (author)
- University of Hull,Weill Cornell Medical College, Qatar
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- Gomez, Maria F. (author)
- Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups
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- Xu, Shang Zhong (author)
- University of Hull
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(creator_code:org_t)
- 2017-12-04
- 2017
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Abstract
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- Impaired albumin reabsorption by proximal tubular epithelial cells (PTECs) has been highlighted in diabetic nephropathy (DN), but little is known about the underlying molecular mechanisms. Here we find that ORAI1-3, are preferentially expressed in PTECs and downregulated in patients with DN. Hyperglycemia or blockade of insulin signaling reduces the expression of ORAI1-3. Inhibition of ORAI channels by BTP2 and diethylstilbestrol or silencing of ORAI expression impairs albumin uptake. Transgenic mice expressing a dominant-negative Orai1 mutant (E108Q) increases albuminuria, and in vivo injection of BTP2 exacerbates albuminuria in streptozotocin-induced and Akita diabetic mice. The albumin endocytosis is Ca2+-dependent and accompanied by ORAI1 internalization. Amnionless (AMN) associates with ORAIs and forms STIM/ORAI/AMN complexes after Ca2+ store depletion. STIM1/ORAI1 colocalizes with clathrin, but not with caveolin, at the apical membrane of PTECs, which determines clathrin-mediated endocytosis. These findings provide insights into the mechanisms of protein reabsorption and potential targets for treating diabetic proteinuria.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Zeng, Bo
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Chen, Gui Lan
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Garcia-Vaz, Elia ...
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Bhandari, Sunil
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Daskoulidou, Nik ...
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Berglund, Lisa M ...
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show more...
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Jiang, Hongni
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Hallett, Thomas
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Zhou, Lu Ping
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Huang, Li
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Xu, Zi Hao
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Nair, Viji
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Nelson, Robert G ...
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Ju, Wenjun
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Kretzler, Matthi ...
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Atkin, Stephen L ...
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Gomez, Maria F.
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Xu, Shang Zhong
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Nature Communica ...
- By the university
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Lund University