title: Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging.
abstract: The majority of cilia are formed and maintained by the highly conserved process of intraflagellar transport (IFT). Mutations in IFT genes lead to ciliary structural defects and systemic disorders termed ciliopathies. Here we show that the severely truncated sensory cilia of hypomorphic IFT mutants in C. elegans transiently elongate during a discrete period of adult aging leading to markedly improved sensory behaviors. Age-dependent restoration of cilia morphology occurs in structurally diverse cilia types and requires IFT. We demonstrate that while DAF-16/FOXO is dispensable, the age-dependent suppression of cilia phenotypes in IFT mutants requires cell-autonomous functions of the HSF1 heat shock factor and the Hsp90 chaperone. Our results describe an unexpected role of early aging and protein quality control mechanisms in suppressing ciliary phenotypes of IFT mutants, and suggest possible strategies for targeting subsets of ciliopathies.
authors.affiliation: Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts.
authors.forename: Astrid
authors.initials: A
authors.lastname: Cornils
authors.affiliation: Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts.
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Maurya
authors.affiliation: Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts.
authors.forename: Lauren
authors.identifier: http://orcid.org/0000-0002-3136-753X
authors.initials: L
authors.lastname: Tereshko
authors.affiliation: School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Julie
authors.initials: J
authors.lastname: Kennedy
authors.affiliation: Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts.
authors.forename: Andrea G
authors.initials: AG
authors.lastname: Brear
authors.affiliation: Department of Biology, Aging Mind and Brain Initiative, University of Iowa, Iowa City, Iowa.
authors.forename: Veena
authors.initials: V
authors.lastname: Prahlad
authors.affiliation: School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Oliver E
authors.initials: OE
authors.lastname: Blacque
authors.affiliation: Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts.
authors.forename: Piali
authors.initials: P
authors.lastname: Sengupta
mesh_terms: D000375:Aging / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics*; D002923:Cilia / Q000235:genetics* / Q000378:metabolism; D000072661:Ciliopathies / Q000235:genetics / Q000628:therapy; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics; D009154:Mutation; D011984:Sensory Receptor Cells / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; C510188:DAF-21 protein, C elegans; D051858:Forkhead Transcription Factors; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C474710:heat shock factor-1, C elegans