title: Identification of G Protein-Coupled Receptors (GPCRs) in Primary Cilia and Their Possible Involvement in Body Weight Control.
abstract: Primary cilia are sensory organelles that harbor various receptors such as G protein-coupled receptors (GPCRs). We analyzed subcellular localization of 138 non-odorant GPCRs. We transfected GPCR expression vectors into NIH3T3 cells, induced ciliogenesis by serum starvation, and observed subcellular localization of GPCRs by immunofluorescent staining. We found that several GPCRs whose ligands are involved in feeding behavior, including prolactin-releasing hormone receptor (PRLHR), neuropeptide FF receptor 1 (NPFFR1), and neuromedin U receptor 1 (NMUR1), localized to the primary cilia. In addition, we found that a short form of dopamine receptor D2 (DRD2S) is efficiently transported to the primary cilia, while a long form of dopamine receptor D2 (DRD2L) is rarely transported to the primary cilia. Using an anti-Prlhr antibody, we found that Prlhr localized to the cilia on the surface of the third ventricle in the vicinity of the hypothalamic periventricular nucleus. We generated the Npy2r-Cre transgenic mouse line in which Cre-recombinase is expressed under the control of the promoter of Npy2r encoding a ciliary GPCR. By mating Npy2r-Cre mice with Ift80 flox mice, we generated Ift80 conditional knockout (CKO) mice in which Npy2r-positive cilia were diminished in number. We found that Ift80 CKO mice exhibited a body weight increase. Our results suggest that Npy2r-positive cilia are important for body weight control.
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, Japan; JST, PRESTO, 3-2 Yamadaoka, Suita, Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Omori
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, Japan; JST, PRESTO, 3-2 Yamadaoka, Suita, Osaka, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Chaya
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, Japan.
authors.forename: Satoyo
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Irie
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Tsujii
authors.affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D001835:Body Weight; D002923:Cilia / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D015430:Weight Gain
chemical_list: C487625:Prlhr protein, mouse; D020033:Protein Isoforms; D017448:Receptors, Dopamine D2; D043562:Receptors, G-Protein-Coupled; C045073:Cre recombinase; D019426:Integrases