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.
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http://dx.doi.org/10.1371/journal.pgen.1006325 | DOI Listing |
Biol Open
September 2024
Neuroscience Program, Lafayette College, Easton, PA 18042, USA.
Proc Natl Acad Sci U S A
August 2024
Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710.
The first steps of vision take place in the ciliary outer segment compartment of photoreceptor cells. The protein composition of outer segments is uniquely suited to perform this function. The most abundant among these proteins is the visual pigment, rhodopsin, whose outer segment trafficking involves intraflagellar transport (IFT).
View Article and Find Full Text PDFMicroPubl Biol
July 2024
Department of Genetics and Human Genetics Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, United States.
Intraflagellar transport (IFT) involves the coordinated transport of molecular motors and other proteins and is required for ciliogenesis and ciliary maintenance. The IFT protein OSM-5 /IFT88 is expressed in a majority of the ciliated neurons in the animal, and mutants exhibit structurally defective cilia. The promoter is commonly used to express genetic constructs in the ciliated neurons.
View Article and Find Full Text PDFJ Cell Sci
July 2024
MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Intraflagellar transport (IFT) is required for ciliary assembly. The IFT machinery comprises the IFT motors kinesin-2 and IFT dynein plus IFT-A and IFT-B complexes, which assemble into IFT trains in cilia. To gain mechanistic understanding of IFT and ciliary assembly, here, we performed an absolute quantification of IFT machinery in Chlamydomonas reinhardtii cilium.
View Article and Find Full Text PDFGenesis
June 2024
Department of Molecular, Cellular and Development Biology, University of Colorado, Boulder, Colorado, USA.
Cilia play a key role in the regulation of signaling pathways required for embryonic development, including the proper formation of the neural tube, the precursor to the brain and spinal cord. Forward genetic screens were used to generate mouse lines that display neural tube defects (NTD) and secondary phenotypes useful in interrogating function. We describe here the L3P mutant line that displays phenotypes of disrupted Sonic hedgehog signaling and affects the initiation of cilia formation.
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