Recruitment of β-Arrestin into Neuronal Cilia Modulates Somatostatin Receptor Subtype 3 Ciliary Localization

• Published in: Molecular and cellular biology Vol. 36; no. 1; pp. 223 - 235
• Main Authors: Green, Jill A., Schmid, Cullen L., Bley, Elizabeth, Monsma, Paula C., Brown, Anthony, Bohn, Laura M., Mykytyn, Kirk
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01-01-2016; American Society for Microbiology
• Subjects: Animals; Arrestins - metabolism; beta-Arrestin 2; beta-Arrestins; Brain - metabolism; Cells, Cultured; Cilia - metabolism; Learning - physiology; Memory - physiology; Mice; Neurons - metabolism; Receptors, Somatostatin - metabolism; Signal Transduction - physiology
• ISSN: 1098-5549; 0270-7306; 1098-5549
• DOI: 10.1128/MCB.00765-15

Primary cilia are essential sensory and signaling organelles present on nearly every mammalian cell type. Defects in primary cilia underlie a class of human diseases collectively termed ciliopathies. Primary cilia are restricted subcellular compartments, and specialized mechanisms coordinate the localization of proteins to cilia. Moreover, trafficking of proteins into and out of cilia is required for proper ciliary function, and this process is disrupted in ciliopathies. The somatostatin receptor subtype 3 (Sstr3) is selectively targeted to primary cilia on neurons in the mammalian brain and is implicated in learning and memory. Here, we show that Sstr3 localization to cilia is dynamic and decreases in response to somatostatin treatment. We further show that somatostatin treatment stimulates β-arrestin recruitment into Sstr3-positive cilia and this recruitment can be blocked by mutations in Sstr3 that impact agonist binding or phosphorylation. Importantly, somatostatin treatment fails to decrease Sstr3 ciliary localization in neurons lacking β-arrestin 2. Together, our results implicate β-arrestin in the modulation of Sstr3 ciliary localization and further suggest a role for β-arrestin in the mediation of Sstr3 ciliary signaling.