title: The role of G protein-coupled receptors in cochlear planar cell polarity.
abstract: Planar cell polarity (PCP) is defined as the coordinated alignment of cell polarity across the tissue plane, which is important for the integration of cells into tissues. One of the best examples of PCP is in the cochlear epithelium. Several core PCP proteins have been identified to play important roles in PCP regulation, in which these proteins form complexes and associate with the cell membrane asymmetrically, mediating intercellular PCP signal transduction. Among the core PCP proteins are two G protein-coupled receptors (GPCRs), Celsr and Frizzled, both of which have been shown to play important roles in cochlear PCP regulation. Celsr and Frizzled genes are expressed in the cochlear sensory epithelium, and Frizzled1, 2, 3 and 6 show asymmetric localizations on the cell membrane of hair cells or supporting cells. In the animal model, Celsr1, Frizzled2 and Frizzled3/6 mutant or knockout mice have profound cochlear PCP deficits. Downstream of GPCR signaling, Gαi was shown to asymmetrically localize on the apical surface of hair cells, together with LGN and mInsc, Gαi controls cochlear PCP in a cell-autonomous way. Inactivity of Gαi, LGN or mInsc results in PCP deficits in the mouse cochlea. We hypothesize that GPCR-Gαi coupling plays a pivotal role in cochlear PCP regulation via connecting the intercellular PCP signals with cell-autonomous PCP machinery. Further investigations are needed to fully understand the mechanism of cochlear PCP regulation.
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan 250012, Shandong, China. Electronic address: sunjinpeng@sdu.edu.cn.
authors.forename: Jinpeng
authors.initials: J
authors.lastname: Sun
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan 250012, Shandong, China.
authors.forename: Daolai
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Shandong University School of Life Sciences, Jinan 250100, Shandong, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medicine, School of Medicine, Duke University, Durham, NC 27705, USA.
authors.forename: Hal
authors.initials: H
authors.lastname: Lin
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan 250012, Shandong, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Shandong University School of Life Sciences, Jinan 250100, Shandong, China. Electronic address: xuzg@sdu.edu.cn.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000818:Animals; D016764:Cell Polarity; D003051:Cochlea / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D043562:Receptors, G-Protein-Coupled
keywords: G protein; GPCR; Hair cells; Inner ear; PCP