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Vsevolod V Gurevich, Sergey A Vishnivetskiy, Seunghyi Kook, Eugenia Gurevich; Self-association does not play a decisive role in the distribution of arrestin-1 in dark-adapted rods. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3029.
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In dark-adapted rods the bulk of arrestin-1 is localized away from the outer segment, where its key binding partner rhodopsin resides. Two factors were proposed to contribute to this counter-intuitive localization of arrestin-1: its binding to microtubules, concentrated in the inner segment, perinucler area, and synaptic terminals, or relatively large size of arrestin-1 dimers and tetramers, which it readily forms at physiological expression level.
We created transgenic mice expressing constitutively monomeric arrestin-1 mutant at different levels, from 10 to ~300% of normal WT arrestin-1 concentration in rods. Since the mutant binds both rhodopsin and microtubules normally, this eliminated a single factor that can contribute to arrestin-1 distribution, its self-association. Arrestin distribution in fixed eyes from dark-adapted WT and transgenic mice expressing this mutant was compared by immunohistochemistry.
The distribution of constitutively monomeric arrestin-1 in dark-adapted rods was remarkably similar to the distribution of WT arrestin-1, which robustly self-associates, so that the majority of arestin-1 complement exists as a tetramer in WT rods in the dark. Self-association-deficient arrestin-1 was largely localized to the inner segments, cell bodies, and synaptic terminals, just like WT protein, with relatively small fraction present in the outer segments.
These data suggest that the size of arestin-1 dimers and tetramers, which are expected to be too large to fit into intra-discal spaces in the outer segments, is not the dominant factor keeping arrestin-1 away from this compartment in the dark. Thus, arrestin-1 distribution in dark-adapted photoreceptors is largely determined by its interactions with to microtubules and/or other binding partners absent in the outer segments. Supported by NIH grant EY011500.
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