title: Functional interplay between cylindromatosis and histone deacetylase 6 in ciliary homeostasis revealed by phenotypic analysis of double knockout mice.
abstract: Cilia are present in most vertebrate tissues with a wide variety of functions, and abnormalities of cilia are linked to numerous human disorders. However, the molecular events underlying ciliary homeostasis are poorly understood. In this study, we generated double knockout (DKO) mice for the deubiquitinase cylindromatosis (CYLD) and histone deacetylase 6 (HDAC6), two critical ciliary regulators. The Cyld/Hdac6 DKO mice were phenotypically normal and showed no obvious variances in weight or behavior compared with their wild-type littermates. Strikingly, Cyld loss-induced ciliary defects in the testis, trachea, and kidney were abrogated in the Cyld/Hdac6 DKO mice. In addition, the diminished α-tubulin acetylation and impaired sonic hedgehog signaling caused by loss of Cyld were largely restored by simultaneous deletion of Hdac6. We further found by immunofluorescence microscopy a colocalization of CYLD and HDAC6 at the centrosome/basal body and, interestingly, loss of Cyld promoted the localization of HDAC6 at the centrosome/basal body. These findings provide physiological insight into the ciliary role of the CYLD/HDAC6 axis and suggest a functional interplay between these two proteins in ciliary homeostasis.
authors.affiliation: Institute of Biomedical Sciences, College of Life Sciences, Key Laboratory of Animal Resistance of Shandong Province, Key Laboratory of Molecular and Nano Probes of The Ministry of Education, Shandong Normal University, Jinan 250014, China.|State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ran
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Yunfan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Dengwen
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute of Biomedical Sciences, College of Life Sciences, Key Laboratory of Animal Resistance of Shandong Province, Key Laboratory of Molecular and Nano Probes of The Ministry of Education, Shandong Normal University, Jinan 250014, China.|State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Biomedical Sciences, College of Life Sciences, Key Laboratory of Animal Resistance of Shandong Province, Key Laboratory of Molecular and Nano Probes of The Ministry of Education, Shandong Normal University, Jinan 250014, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D002923:Cilia / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism / Q000648:ultrastructure; D005347:Fibroblasts / Q000378:metabolism; D005407:Flagella / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D000073864:Histone Deacetylase 6 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D007668:Kidney / Q000378:metabolism / Q000648:ultrastructure; D018345:Mice, Knockout; D010641:Phenotype; D013094:Spermatozoa / Q000378:metabolism; D014132:Trachea / Q000378:metabolism / Q000648:ultrastructure; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000074749:Deubiquitinating Enzyme CYLD
chemical_list: C499033:Hdac6 protein, mouse; D053823:Hedgehog Proteins; D000073864:Histone Deacetylase 6; C465570:Shh protein, mouse; D025521:Tumor Suppressor Proteins; C511601:CYLD protein, mouse; D000074749:Deubiquitinating Enzyme CYLD
keywords: centrosome; cilium; cylindromatosis; histone deacetylase 6; knockout mouse