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Intracellular trafficking of core-glycosylated forms of CFTR
DC Field | Value | Language |
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dc.contributor.author | 지헌영 | - |
dc.date.accessioned | 2015-12-24T08:32:07Z | - |
dc.date.available | 2015-12-24T08:32:07Z | - |
dc.date.issued | 2011 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/133633 | - |
dc.description | Dept. of Medical Science/박사 | - |
dc.description.abstract | The cystic fibrosis transmembrane conductance regulator (CFTR) is an apically localized chloride channel that mediates electrolyte transport in epithelial cells. CFTR is a typical glycoprotein which maturates during the conventional secretory pathway. Mutations in CFTR cause cystic fibrosis and among them, the most prevalent disease-causing mutation is loss of the phenylalanine residue at position 508 (ΔF508). ΔF508 results in protein misfolding and retention in the endoplasmic reticulum (ER). Recent studies suggest that immature, core-glycosylated ΔF508-CFTR can reach the plasma membrane under some conditions. The present study demonstrates that Golgi reassembly stacking protein (GRASP) is required for an unconventional secretory pathway of core-glycosylated CFTR that bypasses the usual route for Golgi-dependent membrane traffic. Integrated molecular and physiological analyses indicate that the core-glycosylated CFTR, but not the mature complex-glycosylated CFTR, can be expressed at the cell surface through a GRASP-dependent mechanism when the conventional route of ER-to-Golgi transport is blocked or ER stress is imposed. In addition, the core-glycosylated CFTR on the plasma membrane can exhibit Cl- channel activity. Overexpression of GRASPs rescued surface expression of ΔF508-CFTR and Cl- channel activity in heterologous systems, and this is mediated by the first PDZ (PSD-95/discs large/ZO-1) domain of GRASP that associates with the C-terminus of CFTR. Furthermore, transgenic expression of GRASP55 restored epithelial Cl- current and rescued mouse survival of ΔF508-CFTR model mice. These results suggest that GRASP-mediated translocation of CFTR could offer a novel therapeutic target for the treatment of CF and could help to understand how therapeutics for ΔF508-CFTR rescue the trafficking of mutant CFTR. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.publisher | Graduate School, Yonsei University | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Intracellular trafficking of core-glycosylated forms of CFTR | - |
dc.title.alternative | Core-glycosylated CFTR의 세포 내 이동경로 탐색 | - |
dc.type | Thesis | - |
dc.identifier.url | https://ymlib.yonsei.ac.kr/catalog/search/book-detail/?cid=CAT000000093500 | - |
dc.contributor.alternativeName | Gee, Heon yung | - |
dc.type.local | Dissertation | - |
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