title: Heat shock transcription factor 1 is required for maintenance of ciliary beating in mice.
abstract: 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.
authors.affiliation: Biochemistry and Molecular Biology and Otolaryngology, Yamaguchi University School of Medicine, Ube 755-8505, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Takaki
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakahari
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yonemura
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Miyata
authors.forename: Naoki
authors.initials: N
authors.lastname: Hayashida
authors.forename: Kaoru
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Richard B
authors.initials: RB
authors.lastname: Vallee
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Mikuriya
authors.forename: Kazuma
authors.initials: K
authors.lastname: Sugahara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamashita
authors.forename: Sachiye
authors.initials: S
authors.lastname: Inouye
authors.forename: Akira
authors.initials: A
authors.lastname: Nakai
mesh_terms: D000818:Animals; D054468:Axoneme / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002908:Chronic Disease; D002923:Cilia / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004805:Ependyma / Q000378:metabolism* / Q000473:pathology; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response / Q000235:genetics; D006849:Hydrocephalus / Q000134:cerebrospinal fluid / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains; D010057:Oviducts / Q000378:metabolism* / Q000473:pathology; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D012852:Sinusitis / Q000134:cerebrospinal fluid / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D018841:HSP90 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D014157:Transcription Factors; D014404:Tubulin