Dynamics of arrestin-rhodopsin interactions: Arrestin and retinal release are directly linked events

Martha E. Sommer, W. Clay Smith, David Farrens

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

In this study, we address the mechanism of visual arrestin release from light-activated rhodopsin using fluorescently labeled arrestin mutants. We find that two mutants, I72C and S251C, when labeled with the small, solvent-sensitive fluorophore monobromobimane, exhibit spectral changes only upon binding light-activated, phosphorylated rhodopsin. Our analysis indicates that these changes are probably due to a burying of the probes at these sites in the rhodopsin-arrestin or phospholipid-arrestin interface. Using a fluorescence approach based on this observation, we demonstrate that arrestin and retinal release are linked and are described by similar activation energies. However, at physiological temperatures, we find that arrestin slows the rate of retinal release ∼2-fold and abolishes the pH dependence of retinal release. Using fluorescence, EPR, and biochemical approaches, we also find intriguing evidence that arrestin binds to a post-Meta II photodecay product, possibly Meta III. We speculate that arrestin regulates levels of free retinal in the rod cell to help limit the formation of damaging oxidative retinal adducts. Such adducts may contribute to diseases like atrophic age-related macular degeneration (AMD). Thus, arrestin may serve to both attenuate rhodopsin signaling and protect the cell from excessive retinal levels under bright light conditions.

Original languageEnglish (US)
Pages (from-to)6861-6871
Number of pages11
JournalJournal of Biological Chemistry
Volume280
Issue number8
DOIs
StatePublished - Feb 25 2005

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Arrestin
Rhodopsin
Light
Fluorescence
Retinal Rod Photoreceptor Cells
Fluorophores
Macular Degeneration
Paramagnetic resonance
Phospholipids
Activation energy
Temperature

ASJC Scopus subject areas

  • Biochemistry

Cite this

Dynamics of arrestin-rhodopsin interactions : Arrestin and retinal release are directly linked events. / Sommer, Martha E.; Smith, W. Clay; Farrens, David.

In: Journal of Biological Chemistry, Vol. 280, No. 8, 25.02.2005, p. 6861-6871.

Research output: Contribution to journalArticle

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