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Corneal dystrophy-associated R124H mutation disrupts TGFBI interaction with Periostin and causes mislocalization to the lysosome

Authors
 Bong-Yoon Kim  ;  James A. Olzmann  ;  Seung-il Choi  ;  So Yeon Ahn  ;  Tae-im Kim  ;  Hyun-Soo Cho  ;  Hwal Suh  ;  Eung Kweon Kim 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.284(29) : 19580-19591, 2009 
Journal Title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN
 0021-9258 
Issue Date
2009
MeSH
Adult ; Amino Acid Substitution ; Animals ; Binding Sites/genetics ; Blotting, Western ; COS Cells ; Cell Adhesion Molecules/genetics ; Cell Adhesion Molecules/metabolism* ; Cell Line ; Cells, Cultured ; Cercopithecus aethiops ; Cornea/cytology ; Cornea/metabolism ; Corneal Dystrophies, Hereditary/genetics ; Corneal Dystrophies, Hereditary/pathology ; Golgi Apparatus/metabolism ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; HeLa Cells ; Humans ; Immunohistochemistry ; Lysosomes/metabolism* ; Microscopy, Fluorescence ; Middle Aged ; Mutation* ; Protein Binding ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/metabolism ; Transfection ; Transforming Growth Factor beta1/genetics ; Transforming Growth Factor beta1/metabolism*
Abstract
The 5q31-linked corneal dystrophies are heterogeneous autosomal-dominant eye disorders pathologically characterized by the progressive accumulation of aggregated proteinaceous deposits in the cornea, which manifests clinically as severe vision impairment. The 5q31-linked corneal dystrophies are commonly caused by mutations in the TGFBI (transforming growth factor-beta-induced) gene. However, despite the identification of the culprit gene, the cellular roles of TGFBI and the molecular mechanisms underlying the pathogenesis of corneal dystrophy remain poorly understood. Here we report the identification of periostin, a molecule that is highly related to TGFBI, as a specific TGFBI-binding partner. The association of TGFBI and periostin is mediated by the amino-terminal cysteine-rich EMI domains of TGFBI and periostin. Our results indicate that the endogenous TGFBI and periostin colocalize within the trans-Golgi network and associate prior to secretion. The corneal dystrophy-associated R124H mutation in TGFBI severely impairs interaction with periostin in vivo. In addition, the R124H mutation causes aberrant redistribution of the mutant TGFBI into lysosomes. We also find that the periostin-TGFBI interaction is disrupted in corneal fibroblasts cultured from granular corneal dystrophy type II patients and that periostin accumulates in TGFBI-positive corneal deposits in granular corneal dystrophy type II (also known as Avellino corneal dystrophy). Together, our findings suggest that TGFBI and periostin may play cooperative cellular roles and that periostin may be involved in the pathogenesis of 5q31-linked corneal dystrophies.
Full Text
https://www.sciencedirect.com/science/article/pii/S0021925819811663
DOI
10.1074/jbc.M109.013607
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Bong Yoon(김봉윤)
Kim, Eung Kweon(김응권) ORCID logo https://orcid.org/0000-0002-1453-8042
Kim, Tae-Im(김태임) ORCID logo https://orcid.org/0000-0001-6414-3842
Suh, Hwal(서활)
Choi, Seung Il(최승일) ORCID logo https://orcid.org/0000-0001-7168-8795
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/104070
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