title: PACRG, a protein linked to ciliary motility, mediates cellular signaling.
abstract: Cilia are microtubule-based organelles that project from nearly all mammalian cell types. Motile cilia generate fluid flow, whereas nonmotile (primary) cilia are required for sensory physiology and modulate various signal transduction pathways. Here we investigate the nonmotile ciliary signaling roles of parkin coregulated gene (PACRG), a protein linked to ciliary motility. PACRG is associated with the protofilament ribbon, a structure believed to dictate the regular arrangement of motility-associated ciliary components. Roles for protofilament ribbon-associated proteins in nonmotile cilia and cellular signaling have not been investigated. We show that PACRG localizes to a small subset of nonmotile cilia in Caenorhabditis elegans, suggesting an evolutionary adaptation for mediating specific sensory/signaling functions. We find that it influences a learning behavior known as gustatory plasticity, in which it is functionally coupled to heterotrimeric G-protein signaling. We also demonstrate that PACRG promotes longevity in C. elegans by acting upstream of the lifespan-promoting FOXO transcription factor DAF-16 and likely upstream of insulin/IGF signaling. Our findings establish previously unrecognized sensory/signaling functions for PACRG and point to a role for this protein in promoting longevity. Furthermore, our work suggests additional ciliary motility-signaling connections, since EFHC1 (EF-hand containing 1), a potential PACRG interaction partner similarly associated with the protofilament ribbon and ciliary motility, also positively regulates lifespan.
authors.affiliation: Department of Molecular Biology and Biochemistry and Centre for Cell Biology, Development and Disease, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
authors.forename: Catrina M
authors.initials: CM
authors.lastname: Loucks
authors.affiliation: Department of Molecular Biology and Biochemistry and Centre for Cell Biology, Development and Disease, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Bialas
authors.affiliation: Department of Cell Biology, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Martijn P J
authors.initials: MP
authors.lastname: Dekkers
authors.affiliation: Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
authors.forename: Denise S
authors.initials: DS
authors.lastname: Walker
authors.affiliation: Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Grundy
authors.affiliation: Department of Molecular Biology and Biochemistry and Centre for Cell Biology, Development and Disease, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Molecular Biology and Biochemistry and Centre for Cell Biology, Development and Disease, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
authors.forename: P Nick
authors.initials: PN
authors.lastname: Inglis
authors.affiliation: School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kida
authors.affiliation: Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
authors.forename: William R
authors.initials: WR
authors.lastname: Schafer
authors.affiliation: School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Oliver E
authors.initials: OE
authors.lastname: Blacque
authors.affiliation: Department of Cell Biology, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Jansen
authors.affiliation: Department of Molecular Biology and Biochemistry and Centre for Cell Biology, Development and Disease, Simon Fraser University, Burnaby, BC V5A 1S6, Canada leroux@sfu.ca.
authors.forename: Michel R
authors.initials: MR
authors.lastname: Leroux
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002923:Cilia / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; D051858:Forkhead Transcription Factors; D018832:Molecular Chaperones; C108831:daf-16 protein, C elegans