title: Heteromerization of ciliary G protein-coupled receptors in the mouse brain.
abstract: Nearly every cell type in the mammalian body projects from its cell surface a primary cilium that provides important sensory and signaling functions. Defects in the formation or function of primary cilia have been implicated in the pathogenesis of many human developmental disorders and diseases, collectively termed ciliopathies. Most neurons in the brain possess cilia that are enriched for signaling proteins such as G protein-coupled receptors and adenylyl cyclase type 3, suggesting neuronal cilia sense neuromodulators in the brain and contribute to non-synaptic signaling. Indeed, disruption of neuronal cilia or loss of neuronal ciliary signaling proteins is associated with obesity and learning and memory deficits. As the functions of primary cilia are defined by the signaling proteins that localize to the ciliary compartment, identifying the complement of signaling proteins in cilia can provide important insights into their physiological roles. Here we report for the first time that different GPCRs can colocalize within the same cilium. Specifically, we found the ciliary GPCRs, melanin-concentrating hormone receptor 1 (Mchr1) and somatostatin receptor 3 (Sstr3) colocalizing within cilia in multiple mouse brain regions. In addition, we have evidence suggesting Mchr1 and Sstr3 form heteromers. As GPCR heteromerization can affect ligand binding properties as well as downstream signaling, our findings add an additional layer of complexity to neuronal ciliary signaling.
authors.affiliation: Department of Pharmacology, College of Medicine, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Green
authors.forename: Chen
authors.initials: C
authors.lastname: Gu
authors.forename: Kirk
authors.initials: K
authors.lastname: Mykytyn
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000502:physiology*; D002478:Cells, Cultured; D002923:Cilia / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D055503:Protein Multimerization; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: C491209:Mchr1 protein, mouse; D017481:Receptors, Somatostatin; C103631:somatostatin receptor 3