Suppression of Mutant Huntingtin Aggregate Formation by Cdk5/p35 through the Effect on Microtubule Stability

Kaminosono, Sayuko; Saito, Taro; Oyama, Fumitaka; Ohshima, Toshio; Asada, Akiko; Nagai, Yoshitaka; Nukina, Nobuyuki; Hisanaga, Shin Ichi

doi:10.1523/jneurosci.0973-08.2008

Cited by 42 publications

(30 citation statements)

References 50 publications

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“…Immunofluorescent Staining and Real-time ObservationCortical neurons were transfected with DsRed, p35-myc, and caFyn by a calcium phosphate method at 5 days in vitro (DIV), as described previously (30), and, 48 h after transfection, neurons were immunostained with anti-myc 4A6, followed by Alexa Fluor 488-conjugated secondary antibodies. Fluorescent images were captured with an LSM510 or LSM710 confocal microscope (Carl Zeiss, Oberkochen, Germany).…”

Section: Methodsmentioning

confidence: 99%

Phosphorylation of Cyclin-dependent Kinase 5 (Cdk5) at Tyr-15 Is Inhibited by Cdk5 Activators and Does Not Contribute to the Activation of Cdk5

Kobayashi

Saito

Sato

et al. 2014

Journal of Biological Chemistry

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Section: Methodsmentioning

confidence: 99%

Phosphorylation of Cyclin-dependent Kinase 5 (Cdk5) at Tyr-15 Is Inhibited by Cdk5 Activators and Does Not Contribute to the Activation of Cdk5

Kobayashi

Saito

Sato

et al. 2014

Journal of Biological Chemistry

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“…COS-7 cells (2 ϫ 10 5 per ml) were grown in DMEM (Sigma) containing 10% FBS and transfected with PolyFect reagent (Qiagen) (Kaminosono et al, 2008).…”

Section: Construction Of Expression Vectors For Tau Proteinsmentioning

confidence: 99%

Regulation of Mitochondrial Transport and Inter-Microtubule Spacing by Tau Phosphorylation at the Sites Hyperphosphorylated in Alzheimer's Disease

Shahpasand

Uemura²,

Saito³

et al. 2012

J. Neurosci.

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172

140

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The microtubule-associated protein Tau is a major component of the neurofibrillary tangles that serve as a neuropathological hallmark of Alzheimer's disease. Tau is a substrate for protein phosphorylation at multiple sites and occurs in tangles in a hyperphosphorylated state. However, the physiological functions of Tau phosphorylation or how it may contribute mechanistically to Alzheimer's pathophysiology are not completely understood. Here, we examined the function of human Tau phosphorylation at three sites, Ser199, Ser202, and Thr205, which together comprise the AT8 sites that mark abnormal phosphorylation in Alzheimer's disease. Overexpression of wild-type Tau or mutated forms in which these sites had been changed to either unphosphorylatable alanines or phosphomimetic aspartates inhibited mitochondrial movement in the neurite processes of PC12 cells as well as the axons of mouse brain cortical neurons. However, the greatest effects on mitochondrial translocation were induced by phosphomimetic mutations. These mutations also caused expansion of the space between microtubules in cultured cells when membrane tension was reduced by disrupting actin filaments. Thus, Tau phosphorylation at the AT8 sites may have meaningful effects on mitochondrial movement, likely by controlling microtubule spacing. Hyperphosphorylation of the AT8 sites may contribute to axonal degeneration by disrupting mitochondrial transport in Alzheimer's disease.

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“…5H). To exclude the possibility of detrimental effects from the overexpression of CDK5, we used a kinase-dead CDK5 (D144N) (44). We confirmed that CDK5 D144N interacted with UCH-L1 at a level comparable with that with CDK5 WT (supplemental Fig.…”

Section: Ectopic Expression Of Cdk5 Attenuates the Interaction Betweementioning

confidence: 57%

Ubiquitin C-terminal Hydrolase L1 (UCH-L1) Acts as a Novel Potentiator of Cyclin-dependent Kinases to Enhance Cell Proliferation Independently of Its Hydrolase Activity

Kabuta

Mitsui

Takahashi

et al. 2013

Journal of Biological Chemistry

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Background: Dysregulation of cell proliferation, usually controlled by cyclin-dependent kinases (CDKs), is a hallmark of cancer.Results: Ubiquitin C-terminal hydrolase L1 (UCH-L1) potentiates CDK activities to enhance cell proliferation. Conclusion: Potentiating CDK activities are a newly identified function of UCH-L1 and are involved in cancer growth. Significance: These findings should lead to a better understanding of, and novel therapies against, cancer.

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Suppression of Mutant Huntingtin Aggregate Formation by Cdk5/p35 through the Effect on Microtubule Stability

Abstract: Huntington's disease (HD) is a polyglutamine [poly(Q)] disease with an expanded poly(Q) stretch in the N terminus of the huntingtin protein (htt).

Cited by 42 publications

References 50 publications

Phosphorylation of Cyclin-dependent Kinase 5 (Cdk5) at Tyr-15 Is Inhibited by Cdk5 Activators and Does Not Contribute to the Activation of Cdk5

Phosphorylation of Cyclin-dependent Kinase 5 (Cdk5) at Tyr-15 Is Inhibited by Cdk5 Activators and Does Not Contribute to the Activation of Cdk5

Regulation of Mitochondrial Transport and Inter-Microtubule Spacing by Tau Phosphorylation at the Sites Hyperphosphorylated in Alzheimer's Disease

Ubiquitin C-terminal Hydrolase L1 (UCH-L1) Acts as a Novel Potentiator of Cyclin-dependent Kinases to Enhance Cell Proliferation Independently of Its Hydrolase Activity

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