scholarly journals Modulation of Actin network and Tau phosphorylation by HDAC6 ZnF UBP domain

2020 ◽  
Author(s):  
Abhishek Ankur Balmik ◽  
Shweta Kishor Sonawane ◽  
Subashchandrabose Chinnathambi
Keyword(s):  
Membrane Integrity ◽  
Neuronal Cell ◽  
Tau Phosphorylation ◽  
Cytoskeleton Organization ◽  
Treatment Conditions ◽  
Actin Cytoskeleton Organization ◽  
Ldh Assay ◽  
Aggresome Formation ◽  
Gsk 3Β

Abstract Background: Microtubule-associated protein Tau undergoes aggregation in Alzheimer`s disease and a group of other related diseases collectively known as Tauopathies. In AD, Tau forms aggregates, which are deposited intracellularly as neurofibrillary tangles. HDAC6 plays an important role in aggresome formation where it recruits poly-ubiquitinated aggregates to the motor protein dynein. Methods: Here, we have studied the effect of HDAC6 ZnF UBP on Tau phosphorylation, ApoE localization, GSK-3β regulation and cytoskeletal organization in neuronal cells by immunofluorescence analysis using fluorescently tagged molecules or antibodies. We have assessed neuronal cell viability and membrane integrity under different treatment conditions by employing MTT and LDH assay respectively. Results: Immunocytochemistry reveals that HDAC6 ZnF UBP can modulate Tau phosphorylation and actin cytoskeleton organization when the cells are exposed to the domain. HDAC6 ZnF UBP treatment to cells does not affect their viability and resulted in enhanced neurite extension and formation of structures similar to podosomes, lamellipodia and podonuts suggesting its role in actin re-organization. Also, HDAC6 treatment showed increased nuclear localization of ApoE and tubulin localization in microtubule organizing centre. Conclusions: Altogether, our studies suggest the regulatory role of this domain in different aspects related to neurodegenerative diseases.

scholarly journals Modulation of Actin network and Tau phosphorylation by HDAC6 ZnF UBP domain

2019 ◽  
Author(s):  
Abhishek Ankur Balmik ◽  
Shweta Kishor Sonawane ◽  
Subashchandrabose Chinnathambi
Keyword(s):  
Nuclear Localization ◽  
Tau Phosphorylation ◽  
Actin Network ◽  
Cytoskeletal Organization ◽  
Protein Tau ◽  
Cytoskeleton Organization ◽  
Actin Cytoskeleton Organization ◽  
Aggresome Formation ◽  
Gsk 3Β

AbstractMicrotubule-associated protein Tau undergoes aggregation in Alzheimer’s disease and a group of other related diseases collectively known as Tauopathies. In AD, Tau forms aggregates, which are deposited intracellularly as neurofibrillary tangles. HDAC6 plays an important role in aggresome formation where it recruits polyubiquitinated aggregates to the motor protein dynein. Here, we have studied the effect of HDAC6 ZnF UBP on Tau phosphorylation, ApoE localization, GSK-3β regulation and cytoskeletal organization in neuronal cells by immunocytochemistry. Immunocytochemistry reveals that HDAC6 ZnF UBP can modulate Tau phosphorylation and actin cytoskeleton organization when the cells are exposed to the domain. HDAC6 ZnF UBP treatment to cells does not affect their viability and resulted in enhanced neurite extension and formation of structures similar to podosomes, lamellipodia and podonuts suggesting its role in actin re-organization. Also, HDAC6 treatment showed increased nuclear localization of ApoE and tubulin localization in microtubule organizing centre. Our studies suggest the regulatory role of this domain in different aspects of neurodegenerative diseases.

scholarly journals The extracellular HDAC6 ZnF UBP domain modulates the actin network and post-translational modifications of Tau

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Abhishek Ankur Balmik ◽  
Shweta Kishor Sonawane ◽  
Subashchandrabose Chinnathambi
Keyword(s):  
Protein Misfolding ◽  
Tau Phosphorylation ◽  
Actin Dynamics ◽  
Histone Deacetylase 6 ◽  
Cytoskeleton Organization ◽  
Actin Cytoskeleton Organization ◽  
Aggresome Formation ◽  
Gsk 3Β ◽  
Misfolding Diseases

Abstract Background Microtubule-associated protein Tau undergoes aggregation in Alzheimer`s disease (AD) and a group of other related diseases collectively known as Tauopathies. In AD, Tau forms aggregates, which are deposited intracellularly as neurofibrillary tangles. Histone deacetylase-6 (HDAC6) plays an important role in aggresome formation, where it recruits polyubiquitinated aggregates to the motor protein dynein. Methods Here, we have studied the effects of HDAC6 ZnF UBP on Tau phosphorylation, ApoE localization, GSK-3β regulation and cytoskeletal organization in neuronal cells by immunocytochemical analysis. This analysis reveals that the cell exposure to the UBP-type zinc finger domain of HDAC6 (HDAC6 ZnF UBP) can modulate Tau phosphorylation and actin cytoskeleton organization. Results HDAC6 ZnF UBP treatment to cells did not affect their viability and resulted in enhanced neurite extension and formation of structures similar to podosomes, lamellipodia and podonuts suggesting the role of this domain in actin re-organization. Also, HDAC6 ZnF UBP treatment caused increase in nuclear localization of ApoE and tubulin localization in microtubule organizing centre (MTOC). Therefore, our studies suggest the regulatory role of this domain in different aspects of neurodegenerative diseases. Upon HDAC6 ZnF UBP treatment, inactive phosphorylated form of GSK-3β increases without any change in total GSK-3β level. Conclusions HDAC6 ZnF UBP was found to be involved in cytoskeletal re-organization by modulating actin dynamics and tubulin localization. Overall, our study suggests that ZnF domain of HDAC6 performs various regulatory functions apart from its classical function in aggresome formation in protein misfolding diseases.

scholarly journals Modulation of Actin Network and Tau Phosphorylation by HDAC6 ZnF UBP  Domain

2020 ◽  
Author(s):  
Balmik Ankur Balmik ◽  
Shweta Kishor Sonawane ◽  
Subashchandrabose Chinnathambi
Keyword(s):  
Nuclear Localization ◽  
Tau Phosphorylation ◽  
Actin Network ◽  
Cytoskeletal Organization ◽  
Protein Tau ◽  
Cytoskeleton Organization ◽  
Actin Cytoskeleton Organization ◽  
Aggresome Formation ◽  
Gsk 3Β

Abstract Microtubule-associated protein Tau undergoes aggregation in Alzheimer`s disease and a group of other related diseases collectively known as Tauopathies. In AD, Tau forms aggregates, which are deposited intracellularly as neurofibrillary tangles. HDAC6 plays an important role in aggresome formation where it recruits polyubiquitinated aggregates to the motor protein dynein. Here, we have studied the effect of HDAC6 ZnF UBP on Tau phosphorylation, ApoE localization, GSK-3β regulation and cytoskeletal organization in neuronal cells by immunocytochemistry. Immunocytochemistry reveals that HDAC6 ZnF UBP can modulate Tau phosphorylation and actin cytoskeleton organization when the cells are exposed to the domain. HDAC6 ZnF UBP treatment to cells does not affect their viability and resulted in enhanced neurite extension and formation of structures similar to podosomes, lamellipodia and podonuts suggesting its role in actin re-organization. Also, HDAC6 treatment showed increased nuclear localization of ApoE and tubulin localization in microtubule organizing centre (MTOC). Our studies suggest the regulatory role of this domain in different aspects of neurodegenerative diseases.

scholarly journals Physiological role of ROCKs in the cardiovascular system

2006 ◽  
Vol 290 (3) ◽  
pp. C661-C668 ◽  
Author(s):  
Kensuke Noma ◽  
Naotsugu Oyama ◽  
James K. Liao
Keyword(s):  
Protein Kinase ◽  
Cardiovascular System ◽  
Vascular Inflammation ◽  
Physiological Role ◽  
Smooth Muscle Contraction ◽  
Kinase Substrate ◽  
Cytoskeleton Organization ◽  
Beneficial Effects ◽  
Actin Cytoskeleton Organization

Rho-associated kinases (ROCKs), the immediate downstream targets of RhoA, are ubiquitously expressed serine-threonine protein kinases that are involved in diverse cellular functions, including smooth muscle contraction, actin cytoskeleton organization, cell adhesion and motility, and gene expression. Recent studies have shown that ROCKs may play a pivotal role in cardiovascular diseases such as vasospastic angina, ischemic stroke, and heart failure. Indeed, inhibition of ROCKs by statins or other selective inhibitors leads to the upregulation and activation of endothelial nitric oxide synthase (eNOS) and reduction of vascular inflammation and atherosclerosis. Thus inhibition of ROCKs may contribute to some of the cholesterol-independent beneficial effects of statin therapy. Currently, two ROCK isoforms have been identified, ROCK1 and ROCK2. Because ROCK inhibitors are nonselective with respect to ROCK1 and ROCK2 and also, in some cases, may be nonspecific with respect to other ROCK-related kinases such as myristolated alanine-rich C kinase substrate (MARCKS), protein kinase A, and protein kinase C, the precise role of ROCKs in cardiovascular disease remains unknown. However, with the recent development of ROCK1- and ROCK2-knockout mice, further dissection of ROCK signaling pathways is now possible. Herein we review what is known about the physiological role of ROCKs in the cardiovascular system and speculate about how inhibition of ROCKs could provide cardiovascular benefits.

Role of GSK-3β activity in motor neuronal cell death induced by G93A or A4V mutant hSOD1 gene

2005 ◽  
Vol 22 (2) ◽  
pp. 301-309 ◽  
Author(s):  
Seong-Ho Koh ◽  
Young-Bae Lee ◽  
Kyung S. Kim ◽  
Hyun-Jung Kim ◽  
Manho Kim ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Gsk 3Β

Inhibition of Wnt and PI3K Signaling Modulates GSK-3β Activity and Induces Morphological Changes in Cortical Neurons: Role of Tau Phosphorylation

2008 ◽  
Vol 33 (8) ◽  
pp. 1599-1609 ◽  
Author(s):  
Octavio Mercado-Gómez ◽  
Karla Hernández-Fonseca ◽  
Alexa Villavicencio-Queijeiro ◽  
Lourdes Massieu ◽  
Jesús Chimal-Monroy ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Morphological Changes ◽  
Tau Phosphorylation ◽  
Pi3k Signaling ◽  
Gsk 3Β

scholarly journals Enhancing calmodulin binding to ryanodine receptor is crucial to limit neuronal cell loss in Alzheimer disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshihide Nakamura ◽  
Takeshi Yamamoto ◽  
Xiaojuan Xu ◽  
Shigeki Kobayashi ◽  
Shinji Tanaka ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Neurodegenerative Disorder ◽  
Neuronal Cell ◽  
Cell Loss ◽  
Tau Phosphorylation ◽  
Pathogenic Role ◽  
Calmodulin Binding ◽  
Neuronal Cell Loss ◽  
Intracellular Ca

AbstractAlzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive neuronal cell loss. Recently, dysregulation of intracellular Ca2+ homeostasis has been suggested as a common proximal cause of neural dysfunction in AD. Here, we investigated (1) the pathogenic role of destabilization of ryanodine receptor (RyR2) in endoplasmic reticulum (ER) upon development of AD phenotypes in AppNL-G-F mice, which harbor three familial AD mutations (Swedish, Beyreuther/Iberian, and Arctic), and (2) the therapeutic effect of enhanced calmodulin (CaM) binding to RyR2. In the neuronal cells from AppNL-G-F mice, CaM dissociation from RyR2 was associated with AD-related phenotypes, i.e. Aβ accumulation, TAU phosphorylation, ER stress, neuronal cell loss, and cognitive dysfunction. Surprisingly, either genetic (by V3599K substitution in RyR2) or pharmacological (by dantrolene) enhancement of CaM binding to RyR2 reversed almost completely the aforementioned AD-related phenotypes, except for Aβ accumulation. Thus, destabilization of RyR2 due to CaM dissociation is most likely an early and fundamental pathogenic mechanism involved in the development of AD. The discovery that neuronal cell loss can be fully prevented simply by stabilizing RyR2 sheds new light on the treatment of AD.

scholarly journals Transcriptomic analysis of the role of Rim101/PacC in the adaptation of Ustilago maydis to an alkaline environment

Microbiology ◽  
2014 ◽  
Vol 160 (9) ◽  
pp. 1985-1998 ◽  
Author(s):  
Eduardo Franco-Frías ◽  
Jose Ruiz-Herrera ◽  
Elva T. Aréchiga-Carvajal
Keyword(s):  
Ustilago Maydis ◽  
Adaptation Mechanism ◽  
Cytoskeleton Organization ◽  
Expression Of Genes ◽  
Actin Cytoskeleton Organization ◽  
Alkaline Conditions ◽  
Polysaccharide Composition ◽  
Microarray Analyses ◽  
Composition Changes

Alkaline pH triggers an adaptation mechanism in fungi that is mediated by Rim101/PacCp, a zinc finger transcription factor. To identify the genes under its control in Ustilago maydis, we performed microarray analyses, comparing gene expression in a wild-type strain versus a rim101/pacC mutation strain of the fungus. In this study we obtained evidence of the large number of genes regulated mostly directly, but also indirectly (probably through regulation of other transcription factors), by Rim101/PacCp, including proteins involved in a large number of physiological activities of the fungus. Our analyses suggest that the response to alkaline conditions under the control of the Pal/Rim pathway involves changes in the cell wall and plasma membrane through alterations in their lipid, protein and polysaccharide composition, changes in cell polarity, actin cytoskeleton organization, and budding patterns. Also as expected, adaptation involves regulation by Rim101/PacC of genes involved in meiotic functions, such as recombination and segregation, and expression of genes involved in ion and nutrient transport, as well as general vacuole functions.

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