TY - JOUR
T1 - Biological role of arrestin-1 oligomerization
AU - Samaranayake, Srimal
AU - Vishnivetskiy, Sergey A.
AU - Shores, Camilla R.
AU - Thibeault, Kimberly C.
AU - Kook, Seunghyi
AU - Chen, Jeannie
AU - Burns, Marie E.
AU - Gurevich, Eugenia V.
AU - Gurevich, Vsevolod V.
N1 - Funding Information:
Received Mar. 31, 2020; revised Sep. 4, 2020; accepted Sep. 8, 2020. Author contributions: J.C., M.E.B., E.V.G., and V.V.G. designed research; S.S., S.A.V., C.R.S., K.C.T., and S.K. performed research; S.S., S.A.V., C.R.S., K.C.T., S.K., M.E.B., E.V.G., and V.V.G. analyzed data; M.E.B., E.V.G., and V.V.G. wrote the paper. *S.S. and S.A.V. contributed equally to this work. The authors declare no competing financial interests. This research was supported by National Institutes of Health (NIH) Grants RO1-EY-011500 and R35-GM-122491 and the Cornelius Vanderbilt Chair (to V.V.G.); and NIH Grants EY-012155 and EY-027193 (to J.C.) and EY-014047 (to M.E.B.). We thank Drs. R.S. Molday and C.M. Craft for monoclonal anti-rhodopsin antibodies and mouse arrestin-1 cDNA, respectively; and Faiza Baameur for generating the clone with mouse Arr1-(F86A, F198A) under control of the rhodopsin promoter for transgenic expression. Correspondence should be addressed to Vsevolod V. Gurevich at vsevolod.gurevich@vanderbilt.edu. https://doi.org/10.1523/JNEUROSCI.0749-20.2020 Copyright © 2020 the authors
PY - 2020/10/14
Y1 - 2020/10/14
N2 - Members of the arrestin superfamily have great propensity of self-association, but the physiological significance of this phenomenon is unclear. To determine the biological role of visual arrestin-1 oligomerization in rod photoreceptors, we expressed mutant arrestin-1 with severely impaired self-association in mouse rods and analyzed mice of both sexes. We show that the oligomerization-deficient mutant is capable of quenching rhodopsin signaling normally, as judged by electroretinography and single-cell recording. Like wild type, mutant arrestin-1 is largely excluded from the outer segments in the dark, proving that the normal intracellular localization is not due the size exclusion of arrestin-1 oligomers. In contrast to wild type, supraphysiological expression of the mutant causes shortening of the outer segments and photoreceptor death. Thus, oligomerization reduces the cytotoxicity of arrestin-1 monomer, ensuring long-term photoreceptor survival.
AB - Members of the arrestin superfamily have great propensity of self-association, but the physiological significance of this phenomenon is unclear. To determine the biological role of visual arrestin-1 oligomerization in rod photoreceptors, we expressed mutant arrestin-1 with severely impaired self-association in mouse rods and analyzed mice of both sexes. We show that the oligomerization-deficient mutant is capable of quenching rhodopsin signaling normally, as judged by electroretinography and single-cell recording. Like wild type, mutant arrestin-1 is largely excluded from the outer segments in the dark, proving that the normal intracellular localization is not due the size exclusion of arrestin-1 oligomers. In contrast to wild type, supraphysiological expression of the mutant causes shortening of the outer segments and photoreceptor death. Thus, oligomerization reduces the cytotoxicity of arrestin-1 monomer, ensuring long-term photoreceptor survival.
KW - Arrestin
KW - Cell death
KW - Oligomerization
KW - Photoreceptor
KW - Rod
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U2 - 10.1523/JNEUROSCI.0749-20.2020
DO - 10.1523/JNEUROSCI.0749-20.2020
M3 - Article
C2 - 32948676
AN - SCOPUS:85093539463
VL - 40
SP - 8055
EP - 8069
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 42
ER -