title: Diverse cell type-specific mechanisms localize G protein-coupled receptors to Caenorhabditis elegans sensory cilia.
abstract: The localization of signaling molecules such as G protein-coupled receptors (GPCRs) to primary cilia is essential for correct signal transduction. Detailed studies over the past decade have begun to elucidate the diverse sequences and trafficking mechanisms that sort and transport GPCRs to the ciliary compartment. However, a systematic analysis of the pathways required for ciliary targeting of multiple GPCRs in different cell types in vivo has not been reported. Here we describe the sequences and proteins required to localize GPCRs to the cilia of the AWB and ASK sensory neuron types in Caenorhabditis elegans. We find that GPCRs expressed in AWB or ASK utilize conserved and novel sequences for ciliary localization, and that the requirement for a ciliary targeting sequence in a given GPCR is different in different neuron types. Consistent with the presence of multiple ciliary targeting sequences, we identify diverse proteins required for ciliary localization of individual GPCRs in AWB and ASK. In particular, we show that the TUB-1 Tubby protein is required for ciliary localization of a subset of GPCRs, implying that defects in GPCR localization may be causal to the metabolic phenotypes of tub-1 mutants. Together, our results describe a remarkable complexity of mechanisms that act in a protein- and cell-specific manner to localize GPCRs to cilia, and suggest that this diversity allows for precise regulation of GPCR-mediated signaling as a function of external and internal context.
authors.affiliation: Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts 02454.
authors.forename: Andrea G
authors.initials: AG
authors.lastname: Brear
authors.affiliation: Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts 02454.
authors.forename: Jason
authors.initials: J
authors.lastname: Yoon
authors.affiliation: Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts 02454.
authors.forename: Martin
authors.initials: M
authors.lastname: Wojtyniak
authors.affiliation: Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts 02454 sengupta@brandeis.edu.
authors.forename: Piali
authors.initials: P
authors.lastname: Sengupta
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D002923:Cilia / Q000502:physiology*; D017124:Conserved Sequence; D008969:Molecular Sequence Data; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000502:physiology; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D043562:Receptors, G-Protein-Coupled; C545587:SRBC-64 protein, C elegans; C504939:tub-1 protein, C elegans
keywords: C. elegans; GPCR; cilia; tubby