Heat shock induces rapid resorption of primary cilia.
Primary cilia are involved in important developmental and disease pathways, such as the regulation of neurogenesis and tumorigenesis. They function as sensory antennae and are essential in the regulation of key extracellular signalling systems. We have investigated the effects of cell stress on primary cilia. Exposure of mammalian cells in vitro, and zebrafish cells in vivo, to elevated temperature resulted in the rapid loss of cilia by resorption. In mammalian cells loss of cilia correlated with a reduction in hedgehog signalling. Heat-shock-dependent loss of cilia was decreased in cells where histone deacetylases (HDACs) were inhibited, suggesting resorption is mediated by the axoneme-localised tubulin deacetylase HDAC6. In thermotolerant cells the rate of ciliary resorption was reduced. This implies a role for molecular chaperones in the maintenance of primary cilia. The cytosolic chaperone Hsp90 localises to the ciliary axoneme and its inhibition resulted in cilia loss. In the cytoplasm of unstressed cells, Hsp90 is known to exist in a complex with HDAC6. Moreover, immediately after heat shock Hsp90 levels were reduced in the remaining cilia. We hypothesise that ciliary resorption serves to attenuate cilia-mediated signalling pathways in response to extracellular stress, and that this mechanism is regulated in part by HDAC6 and Hsp90.
Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ,  UK.
Natalia V
NV
Prodromou
Clare L
CL
Thompson
Daniel P S
DP
Osborn
Kathryn F
KF
Cogger
Rachel
R
Ashworth
Martin M
MM
Knight
Philip L
PL
Beales
J Paul
JP
Chapple
D000818:Animals; D054468:Axoneme / Q000378:metabolism; D002923:Cilia / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response; D053823:Hedgehog Proteins / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D021381:Protein Transport; D015398:Signal Transduction; D013696:Temperature; D015027:Zebrafish / Q000378:metabolism
D018841:HSP90 Heat-Shock Proteins; D053823:Hedgehog Proteins; D006655:Histone Deacetylases