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Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
ARMS2 is a constituent of the extracellular matrix providing a link between familial and sporadic age-related macular degenerations.
Invest. Ophthalmol. Vis. Sci. 51, 79-88 (2010)
SNPs in chromosomal region 10q26 harboring PLEKHA1, ARMS2, and Htra1 showed the strongest association with age-related macular degeneration. Recent evidence suggests that in patients homozygous for the risk allele, the lack of synthesis of the poorly characterized ARMS2 is causative of this disorder. The present study was undertaken to gain an understanding of the genuine (patho)physiological role of this protein. METHODS: ARMS2-interacting proteins were identified by using a yeast two-hybrid system and validated by coprecipitation. Immunofluorescence was applied to reveal the localization of ARMS2 in transfected cells and in human eyes. Western blot analyses were performed on extra- and intracellular fractions of ARMS2-expressing cells to demonstrate the secretion of ARMS2. RESULTS: Contrary to previous reports, this study showed that ARMS2 is a secreted protein that binds several matrix proteins. Notably, ARMS2 directly interacts with fibulin-6 (hemicentin-1). Mutations in the fibulin-6 gene have been demonstrated to cause familial AMD. ARMS2 also interacts with further extracellular proteins, several of which have been implicated in macular dystrophies. Although ARMS2 apparently lacks any classic targeting sequence, it is translocated to the endoplasmic reticulum in cultured cells before secretion. ARMS2 is mostly confined to choroid pillars in human eyes, representing a part of extracellular matrix and corresponding to the principal sites of drusen formation. CONCLUSIONS: The pivotal role of the extracellular matrix in the progression of AMD is underlined by the abnormal deposition of extracellular debris in the macula, observed frequently in affected individuals. The results have shown that ARMS2 may be necessary for proper matrix function.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
complement component 2; factor-b bf; factor-h; metalloproteinases-3 timp-3; tissue inhibitor; cell-adhesion; i collagen; proteins; association; membrane
ISSN (print) / ISBN
0146-0404
e-ISSN
1552-5783
Quellenangaben
Band: 51,
Heft: 1,
Seiten: 79-88
Verlag
Association for Research in Vision and Ophthalmology (ARVO)
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed