HDAC3 and HDAC8 are required for cilia assembly and elongation

Park, Seon-Ah; Yoo, Hyunjeong; Seol, Jae Hong; Rhee, Kunsoo

doi:10.1242/bio.043828

Cited by 5 publications

(5 citation statements)

References 36 publications

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“…The HDAC family of proteins are pleiotropic regulators of cellular function, which includes transcriptional repression, epigenetic modification, and signal transduction (133,150). Importantly, HDACs regulate microtubule disassembly and IFT processes in cilia and are critical in control of cilia length (58,149,213). Building on from this information, it would be valuable to assess whether the use of HDAC inhibitors on ciliated airway epithelial cultures may similarly inhibit RSV replication and maintain cilia expression and function.…”

Section: Respiratory Syncytial Virusmentioning

confidence: 99%

First contact: the role of respiratory cilia in host-pathogen interactions in the airways

Kuek

Lee

2020

American Journal of Physiology-Lung Cellular and Molecular Phys

122

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Respiratory cilia are the driving force of the mucociliary escalator, working in conjunction with secreted airway mucus to clear inhaled debris and pathogens from the conducting airways. Respiratory cilia are also one of the first contact points between host and inhaled pathogens. Impaired ciliary function is a common pathological feature in patients with chronic airway diseases, increasing susceptibility to respiratory infections. Common respiratory pathogens including viruses, bacteria and fungi have been shown to target cilia and/or ciliated airway epithelial cells, resulting in a disruption of mucociliary clearance that may facilitate host infection. Despite being an integral component of airway innate immunity, the role of respiratory cilia and their clinical significance during airway infections is still poorly understood. This review examines the expression, structure, and function of respiratory cilia during pathogenic infection of the airways. This review also discusses specific known points of interaction of bacteria, fungi, and viruses with respiratory cilia function. The emerging biological functions of motile cilia relating to intracellular signaling and their potential immuno-regulatory roles during infection will also be discussed.

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Section: Respiratory Syncytial Virusmentioning

confidence: 99%

First contact: the role of respiratory cilia in host-pathogen interactions in the airways

Kuek

Lee

2020

American Journal of Physiology-Lung Cellular and Molecular Phys

122

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“…Other HDACs have already been described to be involved in cilia disassembly or maintenance, in particular HDAC6, which deacetylates tubulin, thus destabilizing microtubules, leading to cilia disassembly [ 35 ]. Furthermore, HDAC3 and HDAC8 are essential during cilia formation [ 36 ], whereas HDAC2 promotes destruction of cilia [ 37 ]. HDAC7 contains a class II PDZ-binding motif at its C-terminus (Met-Asn-Leu).…”

Section: Resultsmentioning

confidence: 99%

“…In pancreatic ductal adenocarcinoma, HDAC2 enhances the disassembly of primary cilia, likely by promoting Aurora-A expression [ 37 ]. In contrast, HDAC3 and HDAC8 have been reported to positively regulate cilia formation and -morphology in retinal pigment epithelial and kidney proximal tubule cells, although the underlying mechanism is still unclear [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

PATJ inhibits histone deacetylase 7 to control tight junction formation and cell polarity

Fiedler,

Moennig,

Hinrichs

et al. 2023

Cell. Mol. Life Sci.

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The conserved multiple PDZ-domain containing protein PATJ stabilizes the Crumbs-Pals1 complex to regulate apical-basal polarity and tight junction formation in epithelial cells. However, the molecular mechanism of PATJ’s function in these processes is still unclear. In this study, we demonstrate that knockout of PATJ in epithelial cells results in tight junction defects as well as in a disturbed apical-basal polarity and impaired lumen formation in three-dimensional cyst assays. Mechanistically, we found PATJ to associate with and inhibit histone deacetylase 7 (HDAC7). Inhibition or downregulation of HDAC7 restores polarity and lumen formation. Gene expression analysis of PATJ-deficient cells revealed an impaired expression of genes involved in cell junction assembly and membrane organization, which is rescued by the downregulation of HDAC7. Notably, the function of PATJ regulating HDAC7-dependent cilia formation does not depend on its canonical interaction partner, Pals1, indicating a new role of PATJ, which is distinct from its function in the Crumbs complex. By contrast, polarity and lumen phenotypes observed in Pals1- and PATJ-deficient epithelial cells can be rescued by inhibition of HDAC7, suggesting that the main function of this polarity complex in this process is to modulate the transcriptional profile of epithelial cells by inhibiting HDAC7.

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“…Several coenzyme A (CoA) derivatives, including acetyl-CoA, butyryl-CoA, HMG-CoA, and malonyl-CoA, act as allosteric activators of HDACs [ 21 , 24 ]. Moreover, several HDACs, including HDAC2, HDAC3, HDAC6, and HDAC8, control primary cilia assembly and elongation in various tissues [ 25 , 26 , 27 , 28 ]. In this study, we found that treatment with either L-carnitine or acetyl-L-carnitine efficiently promoted primary ciliogenesis in different cells ( Figure 1 ).…”

Section: Discussionmentioning

confidence: 99%

Carnitine Protects against MPP+-Induced Neurotoxicity and Inflammation by Promoting Primary Ciliogenesis in SH-SY5Y Cells

Bae

Kim

et al. 2022

Cells

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Primary cilia help to maintain cellular homeostasis by sensing conditions in the extracellular environment, including growth factors, nutrients, and hormones that are involved in various signaling pathways. Recently, we have shown that enhanced primary ciliogenesis in dopamine neurons promotes neuronal survival in a Parkinson’s disease model. Moreover, we performed fecal metabolite screening in order to identify several candidates for improving primary ciliogenesis, including L-carnitine and acetyl-L-carnitine. However, the role of carnitine in primary ciliogenesis has remained unclear. In addition, the relationship between primary cilia and neurodegenerative diseases has remained unclear. In this study, we have evaluated the effects of carnitine on primary ciliogenesis in 1-methyl-4-phenylpyridinium ion (MPP+)-treated cells. We found that both L-carnitine and acetyl-L-carnitine promoted primary ciliogenesis in SH-SY5Y cells. In addition, the enhancement of ciliogenesis by carnitine suppressed MPP+-induced mitochondrial reactive oxygen species overproduction and mitochondrial fragmentation in SH-SY5Y cells. Moreover, carnitine inhibited the production of pro-inflammatory cytokines in MPP+-treated SH-SY5Y cells. Taken together, our findings suggest that enhanced ciliogenesis regulates MPP+-induced neurotoxicity and inflammation.

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HDAC3 and HDAC8 are required for cilia assembly and elongation

Cited by 5 publications

References 36 publications

First contact: the role of respiratory cilia in host-pathogen interactions in the airways

First contact: the role of respiratory cilia in host-pathogen interactions in the airways

PATJ inhibits histone deacetylase 7 to control tight junction formation and cell polarity

Carnitine Protects against MPP+-Induced Neurotoxicity and Inflammation by Promoting Primary Ciliogenesis in SH-SY5Y Cells

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