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Diversity in arrestin function

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Abstract

The termination of heptahelical receptor signaling is a multilevel process coordinated, in large part, by members of the arrestin family of proteins. Arrestin binding to agonist-occupied receptors promotes desensitization by interrupting receptor-G protein coupling, while simultaneously recruiting machinery for receptor endocytosis, vesicular trafficking, and receptor fate determination. By simultaneously binding other proteins, arrestins also act as ligand-regulated scaffolds that recruit protein and lipid kinase, phosphatase, phosphodiesterase, and ubiquitin ligase activity into receptor-based multiprotein ‘signalsome’ complexes. Arrestin-binding thus ‘switches’ receptors from a transient G protein-coupled state to a persistent arrestin-coupled state that continues to signal as the receptor transits intracellular compartments. While it is clear that signalsome assembly has profound effects on the duration and spatial characteristics of heptahelical receptor signals, the physiologic functions of this novel signaling mechanism are poorly understood. Growing evidence suggests that signalsomes regulate such diverse processes as endocytosis and exocytosis, cell migration, survival, and contractility.

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Acknowledgments

This work was supported by National Institutes of Health Grants DK055524 (L.M.L.) and HL007260 (R.T.K.), the Department of Veterans Affairs Research Enhancement Award Program (L.M.L.), and the Research Service of the Ralph H. Johnson Veterans Affairs Medical Center.

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  1. Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA

    Ryan T. Kendall & Louis M. Luttrell

  2. Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, 29425, USA

    Louis M. Luttrell

  3. Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, 29401, USA

    Louis M. Luttrell

  4. Division of Endocrinology, Diabetes and Medical Genetics, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 816 CSB, MSC 624, Charleston, SC, 29425, USA

    Louis M. Luttrell

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Kendall, R.T., Luttrell, L.M. Diversity in arrestin function. Cell. Mol. Life Sci. 66, 2953–2973 (2009). https://doi.org/10.1007/s00018-009-0088-1

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