Heat shock induces rapid resorption of primary cilia

Advance Online Publication June 20, 2012 doi: 10.1242/?jcs.100545 Natalia V. Prodromou*, Clare Thompson*, Daniel P. S. Osborn, Kathryn F. Cogger, Rachel Ashworth, Martin M. Knight, Philip L. Beales and J. Paul Chapple?Correspondence: Dr Paul Chapple, Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK. Tel: +44 (0) 20 7882 6242; Fax +44 (0) 20 7882 6197; E-mail: j.p.chapple{at}qmul.ac.uk?*These authors contributed equally to this work

Primary cilia are involved in important developmental and disease pathways, such as regulation of neurogenesis and tumorigenesis. They function as sensory antennae and are essential in the regulation of key extracellular signalling systems. Here we investigate 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 cilia loss 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 primary cilia maintenance. 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 remaining cilia. We hypothesise 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.

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