Rhodopsin kinase and arrestin binding control the decay of photoactivated rhodopsin and dark adaptation of mouse rods

Rikard Frederiksen, Soile Nymark, Alexander V. Kolesnikov, Justin D. Berry, Leopold Adler, Yiannis Koutalos, Vladimir J. Kefalov, M. Carter Cornwall

    Research output: Contribution to journalArticleScientificpeer-review

    26 Citations (Scopus)
    20 Downloads (Pure)

    Abstract

    Photoactivation of vertebrate rhodopsin converts it to the physiologically active Meta II (R-star) state, which triggers the rod light response. Meta II is rapidly inactivated by the phosphorylation of C-terminal serine and threonine residues by G-protein receptor kinase (Grk1) and subsequent binding of arrestin 1 (Arr1). Meta II exists in equilibrium with the more stable inactive form of rhodopsin, Meta III. Dark adaptation of rods requires the complete thermal decay of Meta II/Meta III into opsin and all-trans retinal and the subsequent regeneration of rhodopsin with 11-cis retinal chromophore. In this study, we examine the regulation of Meta III decay by Grk1 and Arr1 in intact mouse rods and their effect on rod dark adaptation. We measure the rates of Meta III decay in isolated retinas of wild-type (WT), Grk1-deficient (Grk1(-/-)), Arr1-deficient (Arr1(-/-)), and Arr1-overexpressing (Arr1(ox)) mice. We find that in WT mouse rods, Meta III peaks similar to 6 min after rhodopsin activation and decays with a time constant (tau) of 17 min. Meta III decay slows in Arr1(-/-) rods (tau of similar to 27 min), whereas it accelerates in Arr1(ox) rods (tau of similar to 8 min) and Grk1(-/-) rods (tau of similar to 13 min). In all cases, regeneration of rhodopsin with exogenous 11-cis retinal is rate limited by the decay of Meta III. Notably, the kinetics of rod dark adaptation in vivo is also modulated by the levels of Arr1 and Grk1. We conclude that, in addition to their well-established roles in Meta II inactivation, Grk1 and Arr1 can modulate the kinetics of Meta III decay and rod dark adaptation in vivo.

    Original languageEnglish
    Pages (from-to)1-11
    Number of pages11
    JournalJournal of General Physiology
    Volume148
    Issue number1
    DOIs
    Publication statusPublished - Jul 2016
    Publication typeA1 Journal article-refereed

    Keywords

    • ACTIVE METARHODOPSIN-II
    • BOVINE RHODOPSIN
    • VISUAL PIGMENT
    • PHOSPHORYLATION SITES
    • SIGNALING STATES
    • RETINOID CYCLE
    • VITAMIN-A
    • IN-VIVO
    • LIGHT
    • REGENERATION

    Publication forum classification

    • Publication forum level 2

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