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学科主题临床医学
The Role for HNF-1 beta-Targeted Collectrin in Maintenance of Primary Cilia and Cell Polarity in Collecting Duct Cells
Zhang, Yanling1,2; Wada, Jun1; Yasuhara, Akihiro1; Iseda, Izumi1; Eguchi, Jun1; Fukui, Kenji3; Yang, Qin3,4; Yamagata, Kazuya3; Hiesberger, Thomas5,6; Igarashi, Peter5,6; Zhang, Hong7; Wang, Haiyan7; Akagi, Shigeru8; Kanwar, Yashpal S.8; Makino, Hirofumi1
刊名PLOS ONE
2007-05-02
DOI10.1371/journal.pone.0000414
2期:5
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
资助者JSPS (Japan Society for the Promotion of Science) ; Ministry of Education, Science and Culture, Japan ; Uehara Memorial Foundation ; Scientific Research, Ministry of Education, Science and Culture, Japan ; NIH ; JSPS (Japan Society for the Promotion of Science) ; Ministry of Education, Science and Culture, Japan ; Uehara Memorial Foundation ; Scientific Research, Ministry of Education, Science and Culture, Japan ; NIH
研究领域[WOS]Science & Technology - Other Topics
英文摘要

Collectrin, a homologue of angiotensin converting enzyme 2 (ACE2), is a type I transmembrane protein, and we originally reported its localization to the cytoplasm and apical membrane of collecting duct cells. Recently, two independent studies of targeted disruption of collectrin in mice resulted in severe and general defects in renal amino acid uptake. Collectrin has been reported to be under the transcriptional regulation by HNF-1 alpha, which is exclusively expressed in proximal tubules and localized at the luminal side of brush border membranes. The deficiency of collectrin was associated with reduction of multiple amino acid transporters on luminal membranes. In the current study, we describe that collectrin is a target of HNF-1 beta and heavily expressed in the primary cilium of renal collecting duct cells. Collectrin is also localized in the vesicles near the peri-basal body region and binds to gamma-actin-myosin II-A, SNARE, and polycystin-2-polaris complexes, and all of these are involved in intracellular and ciliary movement of vesicles and membrane proteins. Treatment of mIMCD3 cells with collectrin siRNA resulted in defective cilium formation, increased cell proliferation and apoptosis, and disappearance of polycystin-2 in the primary cilium. Suppression of collectrin mRNA in metanephric culture resulted in the formation of multiple longitudinal cysts in ureteric bud branches. Taken together, the cystic change and formation of defective cilium with the interference in the collectrin functions would suggest that it is necessary for recycling of the primary cilia-specific membrane proteins, the maintenance of the primary cilia and cell polarity of collecting duct cells. The transcriptional hierarchy between HNF-1 beta and PKD (polycystic kidney disease) genes expressed in the primary cilia of collecting duct cells has been suggested, and collectrin is one of such HNF-1 beta regulated genes.

语种英语
所属项目编号17590829 ; 18390249 ; R01DK42921 ; R01DK67565 ; DK28492 ; DK60635 ; 1604241
资助者JSPS (Japan Society for the Promotion of Science) ; Ministry of Education, Science and Culture, Japan ; Uehara Memorial Foundation ; Scientific Research, Ministry of Education, Science and Culture, Japan ; NIH ; JSPS (Japan Society for the Promotion of Science) ; Ministry of Education, Science and Culture, Japan ; Uehara Memorial Foundation ; Scientific Research, Ministry of Education, Science and Culture, Japan ; NIH
WOS记录号WOS:000207445700016
引用统计
被引频次:38[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61197
专题北京大学第一临床医学院_肾脏内科
作者单位1.Okayama Univ, Grad Sch Med, Dept Med & Clin Sci, Okayama, Japan
2.Hebei Med Univ, Hosp 3, Dept Nephrol, Shijiazhuang, Peoples R China
3.Osaka Univ, Grad Sch Med, Dept Metab Med, Osaka, Japan
4.Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA
5.Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA
6.Univ Texas SW Med Ctr Dallas, Div Basic Sci, Dallas, TX 75390 USA
7.Peking Univ, Hosp 1, Inst Nephrol, Div Renal, Beijing 100871, Peoples R China
8.Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA
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Zhang, Yanling,Wada, Jun,Yasuhara, Akihiro,et al. The Role for HNF-1 beta-Targeted Collectrin in Maintenance of Primary Cilia and Cell Polarity in Collecting Duct Cells[J]. PLOS ONE,2007,2(5).
APA Zhang, Yanling.,Wada, Jun.,Yasuhara, Akihiro.,Iseda, Izumi.,Eguchi, Jun.,...&Makino, Hirofumi.(2007).The Role for HNF-1 beta-Targeted Collectrin in Maintenance of Primary Cilia and Cell Polarity in Collecting Duct Cells.PLOS ONE,2(5).
MLA Zhang, Yanling,et al."The Role for HNF-1 beta-Targeted Collectrin in Maintenance of Primary Cilia and Cell Polarity in Collecting Duct Cells".PLOS ONE 2.5(2007).
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