Heat Shock Transcription Factor 1 Is Required for Maintenance of Ciliary Beating in Mice

Biochemistry and Molecular Biology and Otolaryngology, Yamaguchi University School of Medicine, Ube 755-8505, Japan.
Journal of Biological Chemistry (Impact Factor: 4.57). 01/2008; 282(51):37285-92. DOI: 10.1074/jbc.M704562200
Source: PubMed


Heat shock transcription factors (HSFs) maintain protein homeostasis through regulating expression of heat shock proteins, especially in stressed conditions. In addition, HSFs are involved in cellular differentiation and development by regulating development-related genes, as well as heat shock genes. Here, we showed chronic sinusitis and mild hydrocephalus in postnatal HSF1-null mice, which are associated with impaired mucociliary clearance and cerebrospinal flow, respectively. Analysis of ciliary beating revealed that the amplitude of the beating was significantly reduced, and ciliary beat frequencies were lower in the respiratory epithelium, ependymal cells, oviduct, and trachea of HSF1-null mice than those of wild-type mice. Cilia possess a common axonema structure composed of microtubules of alpha- and beta-tubulin. We found a marked reduction in alpha- and ciliary betaiv-tubulin in the HSF1-null cilia, which is developmentally associated with reduced Hsp90 expression in HSF1-null mice. Treatment of the respiratory epithelium with geldanamycin resulted in rapid reduction of ciliary beating in a dose-dependent manner. Furthermore, Hsp90 was physically associated with ciliary betaiv-tubulin, and Hsp90 stabilizes tubulin polymerization in vitro. These results indicate that HSF1 is required to maintain ciliary beating in postnatal mice, probably by regulating constitutive expression of Hsp90 that is important for tubulin polymerization.

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Available from: Naoki Hayashida, Mar 24, 2015
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    • "Ultrastructural studies of Hsf1 respiratory epithelium showed that approximately 10% of cilia were structurally abnormal, with deletion and/or disorganization of the central pair and outer doublet microtubules. The abnormal cilia development in Hsf1 mutants was predicted to result from a secondary decrease in Hsp90 (Heat shock protein 90), which facilitates tubulin stability and polymerization (Takaki et al., 2007). Mice mutant for the Stumpy gene develop hydrocephalus and polycystic kidney disease (Town et al., 2008). "
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    • "This HSF1-mediated induction of Hsp expression is required for the acquisition of thermotolerance (McMillan et al., 1998; Tanabe et al., 1998; Zhang et al., 2002), protection of cells from various pathophysiological conditions such as neurodegenerative and other degenerative diseases (Fujimoto et al., 2005; Cohen et al., 2006; Sakamoto et al., 2006; Tanaka et al., 2007; Steele et al., 2008), and lifespan extension (Hsu et al., 2003; Morley and Morimoto, 2004). HSF1 is also required for the development and maintenance of tissues consisting of neuronal cells (Santos and Saraiva, 2004; Homma et al., 2007), germ cells (Nakai et al., 2000; Izu et al., 2004; Wang et al., 2004), ciliated cells (Takaki et al., 2007), and immune cells (Inouye et al., 2004; Zheng and Li, 2004), but it is not always associated with the regulation of major Hsps. "
    Dataset: mouse HSF3

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    • "The choroid plexus produces cerebrospinal fluid and is circulated through the ventricles of the brain and the subarachnoid space. The ependymal cells lining the ventricular space are known to possess motile cilia, and that defects in these motile cilia can contribute to an obstruction of CSF flow leading to hydrocephalus [62], [63], [64], [65]. In contrast, the murine ciliopathy model Tg737orpk demonstrated hydrocephalus before formation of motile cilia in the ependymal cells [66], implicating defects in choroid plexus function (such as increased CSF production) as a primary event in these animals. "
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