HDAC6 is a microtubule-associated deacetylase

Hubbert, Charlotte; Guardiola, Amaris R.; Shao, Rong; Kawaguchi, Yoshiharu; Ito, Akihiro; Nixon, Andrew B.; Yoshida, Minoru; Wang, Xiaofan; Yao, Tso‐Pang

doi:10.1038/417455a

Cited by 2,032 publications

(2,053 citation statements)

References 21 publications

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“…Cytoplasmic HDAC6 shows striking co-localization with the microtubule network [87,88]. Acetylation of a-tubulin, at lysine 40, has been used as a marker of microtubule stability [89].…”

Section: Tigs 54mentioning

confidence: 99%

“…Acetylation of a-tubulin, at lysine 40, has been used as a marker of microtubule stability [89]. HDAC6 functions as a specific tubulin deacetylase in vivo, and purified HDAC6 deacetylates a-tubulin in assembled microtubules in vitro [87,88]. HDAC6 overexpression promotes chemotactic cell movement, a cellular function dependent on microtubules.…”

Section: Tigs 54mentioning

confidence: 99%

“…4) [56]. Suppression of either HDAC6 or SIRT2 mediated by siRNA leads to a relative hyperacetylation of a-tubulin acetylation in vivo [56,87,88]. The identification of specific enzymes mediating tubulin deacetylation should allow further work to proceed on the role of this modification in microtubule dynamics and functions.…”

Section: Tigs 54mentioning

confidence: 99%

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Class II histone deacetylases: versatile regulators

2003

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Histone acetylation and deacetylation play essential roles in modifying chromatin structure and regulating gene expression in eukaryotes. Histone deacetylases (HDACs) catalyze the deacetylation of lysine residues in the histone N-terminal tails and are found in large multiprotein complexes with transcriptional co-repressors. Human HDACs are grouped into three classes based on their similarity to known yeast factors: class I HDACs are similar to the yeast transcriptional repressor yRPD3, class II HDACs to yHDA1 and class III HDACs to ySIR2. In this review, we focus on the biology of class II HDACs. These newly discovered enzymes have been implicated as global regulators of gene expression during cell differentiation and development. We discuss their emerging biological functions and the molecular mechanisms by which they are regulated.

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“…Cytoplasmic HDAC6 shows striking co-localization with the microtubule network [87,88]. Acetylation of a-tubulin, at lysine 40, has been used as a marker of microtubule stability [89].…”

Section: Tigs 54mentioning

confidence: 99%

Section: Tigs 54mentioning

confidence: 99%

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Class II histone deacetylases: versatile regulators

2003

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“…Indeed, loss of HDAC6 causes a reduction in cell motility both in NIH/3T3 fibroblasts [4,5] and lymphocytes [24]. HDAC6 may thus be a cellular homeostasis surveillance factor.…”

Section: Hdac6 Regulates Mitochondrial Metabolic Activity In the Cytomentioning

confidence: 99%

Depression of mitochondrial metabolism by downregulation of cytoplasmic deacetylase, HDAC6

et al. 2012

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a b s t r a c tMitochondria perform multiple functions critical to the maintenance of cellular homeostasis. Here we report that the downregulation of histone deacetylase 6 (HDAC6) causes a reduction in the net activity of mitochondrial enzymes, including respiratory complex II and citrate synthase. HDAC6 deacetylase and ubiquitin-binding activities were both required for recovery of reduced mitochondrial metabolic activity due to the loss of HDAC6. Hsp90, a substrate of HDAC6, localizes to mitochondria and partly mediates the regulation of mitochondrial metabolic activity by HDAC6. Our finding suggests that HDAC6 regulates mitochondrial metabolism and might serve as a cellular homeostasis surveillance factor.

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“…Histone deacetylase 6 (HDAC6), a cytosolic member of class II HDACs 18 , is responsible for deacetylating both tubulin 19 and tau 16 . Intriguingly, neurons in which HDAC6 were knocked down lose the axonal initial segment (AIS) 20 , a trafficking barrier important for maintaining the polarized localization of axonal proteins, although the mechanism remains unknown.…”

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confidence: 99%

HDAC6 and RhoA are novel players in Abeta-driven disruption of neuronal polarity

et al. 2015

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Maintenance of neuronal polarity and regulation of cytoskeletal dynamics are vital during development and to uphold synaptic activity in neuronal networks. Here we show that soluble b-amyloid (Ab) disrupts actin and microtubule (MT) dynamics via activation of RhoA and inhibition of histone deacetylase 6 (HDAC6) in cultured hippocampal neurons. The contact of Ab with the extracellular membrane promotes RhoA activation, leading to growth cone collapse and neurite retraction, which might be responsible for hampered neuronal pathfinding and migration in Alzheimer's disease (AD). The inhibition of HDAC6 by Ab increases the level of heterodimeric acetylated tubulin and acetylated tau, both of which have been found altered in AD. We also find that the loss of HDAC6 activity perturbs the integrity of axon initial segment (AIS), resulting in mislocalization of ankyrin G and increased MT instability in the AIS concomitant with loss of polarized localization of tau and impairment of action potential firing.

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HDAC6 is a microtubule-associated deacetylase

Cited by 2,032 publications

References 21 publications

Class II histone deacetylases: versatile regulators

Class II histone deacetylases: versatile regulators

Depression of mitochondrial metabolism by downregulation of cytoplasmic deacetylase, HDAC6

HDAC6 and RhoA are novel players in Abeta-driven disruption of neuronal polarity

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