Heat shock induces rapid resorption of primary cilia

Abstract

SummaryPrimary 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.

NudC regulates actin dynamics and ciliogenesis by stabilizing cofilin 1

“…Inhibition of Hsp90 activity by geldanamycin significantly suppressed cilia assembly (Supplementary information, Figure S15), which is consistent with the previous study [39]. Unexpectedly, geldanamycin treatment had no significant effect on the protein level of cofilin 1 (Supplementary information, Figure S16), implying that NudC may stabilize cofilin 1 via an Hsp90-independent pathway.…”

Hsp90α forms a stable complex at cilia neck for signal molecules interaction in cilia-mediated IGF-1 receptor signaling

“…Cilia excision, which occurs in response to environmental stresses such as heat shock, usually occurs at this transition neck region (Quarmby, 2004). The rapid resorption of primary cilia that is induced by heat shock is regulated, at least in part, by the 90-kDa heat shock protein, Hsp90 (Prodromou et al, 2012).…”

An inducible transgene expression system for zebrafish and chick

“…Additionally, heat shock affords no tissue specificity without additional engineering of dedicated transgenic lines such as a enhancer or UAS-driven, floxed STOP-transgene constructs (Thummel et al, 2005;Hans et al, 2009) to provide an intersectional expression system. These approaches are complex, and drawbacks include the detrimental effect of heat-shock on primary cilia (Prodromou et al, 2012), and the accelerated development at higher temperatures, a confounding variable when studying a dynamic system or a short-lived biological phenomenon.…”