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Lysosomal trafficking of TGFBIp via caveolae-mediated endocytosis

Authors
 Seung-il Choi  ;  Yong-Sun Maeng  ;  Tae-im Kim  ;  Yangsin Lee  ;  Yong-Sun Kim  ;  Eung Kweon Kim 
Citation
 PLoS One, Vol.10(4) : e0119561, 2015 
Journal Title
 PLoS One 
ISSN
 1932-6203 
Issue Date
2015
Abstract
Transforming growth factor-beta-induced protein (TGFBIp) is ubiquitously expressed in the extracellular matrix (ECM) of various tissues and cell lines. Progressive accumulation of mutant TGFBIp is directly involved in the pathogenesis of TGFBI-linked corneal dystrophy. Recent studies reported that mutant TGFBIp accumulates in cells; however, the trafficking of TGFBIp is poorly understood. Therefore, we investigated TGFBIp trafficking to determine the route of its internalization and secretion and to elucidate its roles in the pathogenesis of granular corneal dystrophy type 2 (GCD2). Our data indicate that newly synthesized TGFBIp was secreted via the endoplasmic reticulum/Golgi-dependent secretory pathway, and this secretion was delayed in the corneal fibroblasts of patients with GCD2. We also found that TGFBIp was internalized by caveolae-mediated endocytosis, and the internalized TGFBIp accumulated after treatment with bafilomycin A1, an inhibitor of lysosomal degradation. In addition, the proteasome inhibitor MG132 inhibits the endocytosis of TGFBIp. Co-immunoprecipitation revealed that TGFBIp interacted with integrin αVβ3. Moreover, treatment with arginine-glycine-aspartic acid (RGD) tripeptide suppressed the internalization of TGFBIp. These insights on TGFBIp trafficking could lead to the identification of novel targets and the development of new therapies for TGFBI-linked corneal dystrophy.
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DOI
10.1371/journal.pone.0119561
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Corneal Dystrophy Research Institute (각막이상증연구소) > 1. Journal Papers
Yonsei Authors
김응권(Kim, Eung Kweon) ORCID logo https://orcid.org/0000-0002-1453-8042
김태임(Kim, Tae Im) ORCID logo https://orcid.org/0000-0001-6414-3842
맹용선(Maeng, Yong Sun) ORCID logo https://orcid.org/0000-0003-1694-8405
최승일(Choi, Seung Il) ORCID logo https://orcid.org/0000-0001-7168-8795
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/139975
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