Cone Arrestin: Deciphering the Structure and Functions of Arrestin 4 in Vision
Cone arrestin (Arr4) was discovered 20 years ago as a human X-chromosomal gene that is highly expressed in pinealocytes and cone photoreceptors. Subsequently, specific antibodies were developed to identify Arr4 and to distinguish cone photoreceptor morpho
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Contents 1 Discovery of Cone Arrestin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Cellular Localization and Expression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Evolution of Cone Arrestin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Crystal Structure and G Protein-Coupled Receptor Binding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Role in S- and M-Cone Opsin Shutoff . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Other Potential Binding Partners of Arr4 Are Identified . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Role in Visual Perception Phenotypes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Potential Therapeutic Use of Cone Arrestin Promoter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Abstract Cone arrestin (Arr4) was discovered 20 years ago as a human X-chromosomal gene that is highly expressed in pinealocytes and cone photoreceptors. Subsequently, specific antibodies were developed to identify Arr4 and to distinguish cone photoreceptor morphology in health and disease states. These reagents were used to demonstrate Arr4 translocation from cone inner segments in the dark to outer segments with light stimulation, similarly to Arrestin 1 (Arr1) translocation in rod photoreceptors. A decade later, the Arr4 crystal structure was solved, which provided more clues about Arr4’s mechanisms of action. With the creation of genetically engineered visual arrestin knockout mice, one critical function of Arr4 was clarified. In single living cones, both visual arrestins bind to light-activated, G protein receptor kinase 1 (Grk1) phosphorylated cone opsins to desensitize them, and in their absence, mouse cone pigment shutoff is delayed. Still under investigation are additional functions; however, it is clear that Arr4 has non-opsin-binding partners and diverse synaptic roles, including cellular anchoring C.M. Craft (*) • J.D. Deming Mary D. Allen Laboratory for Vision Research, Doheny Eye Institute, Departments of Ophthalmology and Cell and Neurobiology, , Keck School of Medicine, University of Southern California, 1355 San Pablo Street, DVRC 405, Los Angeles, CA 90033, 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_6, © Springer-Verlag Berlin Heidelberg 2014
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