2004 Fiscal Year Final Research Report Summary
Identification of Novel ACE2 homologue, collectrin, and its role in renal organogenesis and progressive renal failure.
| Project/Area Number |
14571025
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
WADA Jun Okayama University, University Hospital, Assistant Professor, 医学部・歯学部附属病院, 講師 (30294408)
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| Co-Investigator(Kenkyū-buntansha) |
MAKINO Hirofumi Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (50165685)
SHIKATA Kenichi Okayama University, University Hospital, Assistant Professor, 医学部・歯学部附属病院, 講師 (00243452)
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| Project Period (FY) |
2002 – 2004
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| Keywords | collectrin / ACE2 / HNF-1β / renal organogenesis / glomerulosclerosis |
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| Research Abstract |
Collectrin, a novel homologue of angiotensin converting enzyme-related carboxypeptidase (ACE2), was identified in 5/6 ablated kidneys at hypertrophic phase (Zhang H et al. J Biol Chem 276(20),17132-17139,2001). By using an animal model of partial nephrectomy, several differentially expressed genes were isolated by the PCR-based cDNA-subtraction method (Zhang H et al. Kidney Int 56(2),549-558,1999). Because one of these genes was kidney-specific and highly localized to the collecting ducts, it was designated as collectrin. The sequence analyses revealed that collectrin with 222 amino acids has an apparent signal peptide and a transmembrane domain (black box in figure shown below) ; the sequence is conserved in mouse, rat and human and shared 81.9% identity. Human collectrin has 47.8% identity with non-catalytic extracellular and cytosolic domains of ACE2 (white box in figure), however, unlike ACE and ACE2, collectrin lacks active dipeptidyl carboxypeptidase catalytic domains. Interestingly, ACE2 and collectrin are located close to each other in the same chromosomal region (Xp22) and whereas ACE is located chromosome 17. The collectrin mRNA transcripts are expressed exclusively in the kidney. In situ hybridization reveals its mRNA expression in renal collecting ducts and immunohistochemistry shows it is localized to the luminal surface and cytoplasm of collecting ducts.
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Proc Natl Acad Sci U S A 102(30)
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[Journal Article] The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formation.2005
Author(s)
Fukui K, Yang Q, Cao Y, Takahashi N, Hatakeyama H, Wang H, Wada J, Zhang Y, Marselli L, Nammo T, Yoneda K, Onishi M, Higashiyama S, Matsuzawa Y, Gonzlez FJ, Weir GC, Kasai H, Shimomura I, Miyagawa J, Wollheim CB, Yamagata K
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Description
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