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G. Wang, W. K. Scott, J. L. Haines, M. A. Pericak-Vance; Cytoskeleton Associated ARMS2 in Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2660.
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Age-related macular degeneration (AMD) is the main cause of visual impairment and blindness in developed countries. Genetic variations in the ARMS2 gene at the 10q26 locus have been consistently shown to contribute to AMD risk. However, the mechanism by which ARMS2 influences development of AMD remains to be elucidated. Recently, ARMS2 was reported to localize within mitochondria, suggesting its function may be involved in mitochondria mediated energy metabolism, oxidative stress and apoptosis. This study is designed to explore the detailed function of ARMS2.
We developed antibodies specifically targeting the human ARMS2 N-terminus and C-terminus for immunostaining of ARPE-19 cells. We also expressed ARMS2 in COS7 cells.
We found that endogenous ARMS2 localizes to the perinuclear region in retina epithelial ARPE-19 cells. There was little evidence of ARMS2 co-localization with mitochondria stained with mitoTracker. In the present experiment, ARMS2 associated almost completely with the cytoskeleton. This finding was further confirmed by immunostaining exogenous ARMS2 using anti-His tag and anti-V5-tag antibodies in COS7 cells. Additionally, ARMS2 was found to lack any known mitochondrial targeting motifs.
We suggest that ARMS2 is associated with the cytoskeleton and that genetic variation in ARMS2 may influence risk of AMD through impairment of cytoskeleton rearrangement.
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