The Physiological Roles of Arrestin-1 in Rod Photoreceptor Cells
Arrestin-1 is the second most abundant protein in rod photoreceptors and is nearly equimolar to rhodopsin. Its well-recognized role is to “arrest” signaling from light-activated, phosphorylated rhodopsin, a prototypical G protein-coupled receptor. In doin
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Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Arrestin-1 Rhodopsin Interaction: Structure/Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 The Concentration of Arrestin in Rods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Arrestin-1 Translocation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Functional Comparison of Arrestin-1 and Arrestin-4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Arrestin-1 in Health and Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Arrestin-1 Protects the Retina Against Light Damage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Functional Defect in Arrestin-1 Leads to Oguchi Disease in Humans . . . . . . . . . . . . . . . 3.3 Persistent Rhodopsin/Arrestin-1 Complex is Toxic to Rods . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Functional Comparison Between Arrestin-1 and ß-Arrestins . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Abstract Arrestin-1 is the second most abundant protein in rod photoreceptors and is nearly equimolar to rhodopsin. Its well-recognized role is to “arrest” signaling from light-activated, phosphorylated rhodopsin, a prototypical G protein-coupled receptor. In doing so, arrestin-1 plays a key role in the rapid recovery of the light response. Arrestin-1 exists in a basal conformation that is stabilized by two independent sets of intramolecular interactions. The intramolecular constraints are disrupted by encountering (1) active conformation of the receptor (R*) and (2) receptor-attached phosphates. Requirement for these two events ensures its highly specific high-affinity binding to phosphorylated, light-activated rhodopsin (P-R*). In the dark-adapted state, the basal form is further organized into dimers and tetramers. Emerging data suggest pleiotropic roles of arrestin-1 beyond the functional range of rod cells. These include light-induced arrestin-1 translocation from the inner segment to the outer segment, a process that may be protective J. Chen (*) Department of Cell and Neurobiology, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA e-mail: [email protected] V.V. Gurevich (ed.), Arrestins - Pharmacology and Therapeutic Potential, Handbook of Experimental Pharmacology 219, DOI 10.1007/978-3-642-41199-1_4, © Springer-Verlag Berlin Heidelberg 2014
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against cellular damage incurred by constitutive signaling.
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