Journal article
Rapid degeneration of rod photoreceptors expressing self-association-deficient arrestin-1 mutant
Cellular signalling, v 25(12), pp 2613-2624
Dec 2013
PMID: 24012956
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Arrestin-1 binds light-activated phosphorhodopsin and ensures timely signal shutoff. We show that high transgenic expression of an arrestin-1 mutant with enhanced rhodopsin binding and impaired oligomerization causes apoptotic rod death in mice. Dark rearing does not prevent mutant-induced cell death, ruling out the role of arrestin complexes with light-activated rhodopsin. Similar expression of WT arrestin-1 that robustly oligomerizes, which leads to only modest increase in the monomer concentration, does not affect rod survival. Moreover, WT arrestin-1 co-expressed with the mutant delays retinal degeneration. Thus, arrestin-1 mutant directly affects cell survival via binding partner(s) other than light-activated rhodopsin. Due to impaired self-association of the mutant its high expression dramatically increases the concentration of the monomer. The data suggest that monomeric arrestin-1 is cytotoxic and WT arrestin-1 protects rods by forming mixed oligomers with the mutant and/or competing with it for the binding to non-receptor partners. Thus, arrestin-1 self-association likely serves to keep low concentration of the toxic monomer. The reduction of the concentration of harmful monomer is an earlier unappreciated biological function of protein oligomerization.
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•Monomeric arrestin-1 is cytotoxictoxic•Robust self-association of arestin-1 is a cytoprotective mechanism•Monomer toxicity might explain low expression of arrestin-4 in cones•Monomer toxicity might explain self-association of non-visual arrestins
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Details
- Title
- Rapid degeneration of rod photoreceptors expressing self-association-deficient arrestin-1 mutant
- Creators
- Xiufeng Song - Vanderbilt UniversityJungwon Seo - Vanderbilt UniversityFaiza Baameur - Vanderbilt UniversitySergey A. Vishnivetskiy - Vanderbilt UniversityQiuyan Chen - Vanderbilt UniversitySeunghyi Kook - Vanderbilt UniversityMiyeon Kim - University of California Los AngelesEvan K. Brooks - University of California Los AngelesChristian Altenbach - University of California Los AngelesYuan Hong - Vanderbilt UniversitySusan M. Hanson - Vanderbilt UniversityMaria C. Palazzo - Vanderbilt UniversityJeannie Chen - University of Southern CaliforniaWayne L. Hubbell - University of California Los AngelesEugenia V. Gurevich - Vanderbilt UniversityVsevolod V. Gurevich - Vanderbilt University
- Publication Details
- Cellular signalling, v 25(12), pp 2613-2624
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Mathematics
- Web of Science ID
- WOS:000328179800027
- Scopus ID
- 2-s2.0-84884392198
- Other Identifier
- 991019173457504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology