Primary cilia are involved in important developmental anddisease pathways, such as the regulation of neurogenesisand tumorigenesis. They function as sensory antennae andare essential in the regulation of key extracellular signallingsystems. In this study we investigate the effects of cellstress on primary cilia. Exposure of mammalian cells invitro, and zebrafish cells in vivo, to elevated temperatureresulted in the rapid loss of cilia by resorption. In mammaliancells cilia loss correlated with a reduction in liganddependent hedgehog signalling. Heat shock dependentloss of cilia was decreased in cells where histone deacetylases(HDACs) were inhibited, suggesting resorption ismediated by HDAC6 which localises to ciliary axonemes.The rate of cilia resorption was reduced in thermotolerantcells. This implies a role for molecular chaperones in primarycilia maintenance. The cytosolic chaperone Hsp90localised to the ciliary axoneme and its inhibition resultedin cilia loss. In the cytoplasm of unstressed cells Hsp90 isknown to exist in a complex with HDAC6. Immediatelyafter heat shock Hsp90 levels were reduced in remainingciliary axonemes. We hypothesise that cilia resorption inresponse to heat shock is regulated by the disassembly ofan HDAC6/Hsp90 complex and would serve to attenuatecilia mediated signalling pathways and reduce the translationalload on the cell in times of stress.
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