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DOI | 10.1038/s41467-018-03543-y |
ORAI channels are critical for receptor-mediated endocytosis of albumin | |
Zeng, Bo1,2,3; Chen, Gui-Lan1,2,3; Garcia-Vaz, Eliana4; Bhandari, Sunil5,6; Daskoulidou, Nikoleta1; Berglund, Lisa M.4; Jiang, Hongni1; Hallett, Thomas1; Zhou, Lu-Ping2,3; Huang, Li2,3; Xu, Zi-Hao2,3; Nair, Viji7,8; Nelson, Robert G.9; Ju, Wenjun7,8; Kretzler, Matthias7,8; Atkin, Stephen L.1,10; Gomez, Maria F.4; Xu, Shang-Zhong1 | |
2017-12-04 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | England; Peoples R China; Sweden; USA; Qatar |
英文摘要 | 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 down-regulated 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. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000417029900010 |
WOS关键词 | TUBULAR-AGGREGATE MYOPATHY ; OPERATED CA2+ ENTRY ; PROXIMAL TUBULE ; DIABETIC-NEPHROPATHY ; MESANGIAL CELLS ; CRAC CHANNEL ; CONSTITUTIVE ACTIVATION ; EPITHELIAL-CELLS ; KIDNEY-DISEASE ; HIGH GLUCOSE |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203730 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Hull, Hull York Med Sch, Ctr Cardiovasc & Metab Res, Kingston Upon Hull HU6 7RX, N Humberside, England; 2.Southwest Med Univ, Key Lab Med Electrophysiol, Minist Educ, Luzhou 646000, Peoples R China; 3.Southwest Med Univ, Inst Cardiovasc Res, Luzhou 646000, Peoples R China; 4.Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci Malmo, S-21428 Malmo, Malmo, Sweden; 5.Hull & East Yorkshire Hosp NHS Trust, Hull Royal Infirm, Dept Renal Med, Kingston Upon Hull HU3 2JZ, N Humberside, England; 6.Hull & East Yorkshire Hosp NHS Trust, Hull Royal Infirm, Hull York Med Sch, Kingston Upon Hull HU3 2JZ, N Humberside, England; 7.Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA; 8.Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA; 9.NIDDK, Chron Kidney Dis Sect, NIH, Phoenix, AZ 85014 USA; 10.Weill Cornell Med Coll Qatar, Doha 24144, Qatar |
推荐引用方式 GB/T 7714 | Zeng, Bo,Chen, Gui-Lan,Garcia-Vaz, Eliana,et al. ORAI channels are critical for receptor-mediated endocytosis of albumin[J]. NATURE COMMUNICATIONS,2017,8. |
APA | Zeng, Bo.,Chen, Gui-Lan.,Garcia-Vaz, Eliana.,Bhandari, Sunil.,Daskoulidou, Nikoleta.,...&Xu, Shang-Zhong.(2017).ORAI channels are critical for receptor-mediated endocytosis of albumin.NATURE COMMUNICATIONS,8. |
MLA | Zeng, Bo,et al."ORAI channels are critical for receptor-mediated endocytosis of albumin".NATURE COMMUNICATIONS 8(2017). |
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