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 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):  
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 Hypoxia-Induced miR-675-5p Supports β-Catenin Nuclear Localization by Regulating GSK3-β  Activity in Colorectal Cancer Cell Lines

2020 ◽  
Vol 21 (11) ◽  
pp. 3832 ◽  
Author(s):  
Laura Saieva ◽  
Maria Magdalena Barreca ◽  
Chiara Zichittella ◽  
Maria Giulia Prado ◽  
Marco Tripodi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Nuclear Localization ◽  
Cancer Cell Lines ◽  
Colorectal Cancer Cell ◽  
Non Coding Rna ◽  
Colorectal Cancer Cell Lines ◽  
Gsk 3Β

The reduction of oxygen partial pressure in growing tumors triggers numerous survival strategies driven by the transcription factor complex HIF1 (Hypoxia Inducible Factor-1). Recent evidence revealed that HIF1 promotes rapid and effective phenotypic changes through the induction of non-coding RNAs, whose contribution has not yet been fully described. Here we investigated the role of the hypoxia-induced, long non-coding RNA H19 (lncH19) and its intragenic miRNA (miR-675-5p) into HIF1-Wnt crosstalk. During hypoxic stimulation, colorectal cancer cell lines up-regulated the levels of both the lncH19 and its intragenic miR-675-5p. Loss of expression experiments revealed that miR-675-5p inhibition, in hypoxic cells, hampered β-catenin nuclear localization and its transcriptional activity, while lncH19 silencing did not induce the same effects. Interestingly, our data revealed that miRNA inhibition in hypoxic cells restored the activity of Glycogen Synthase Kinase 3β (GSK-3β) reducing the amount of P-Ser9 kinase, thus unveiling a role of the miR-675-5p in controlling GSK-3β activity. Bioinformatics analyses highlighted the serine/threonine-protein phosphatases PPP2CA, responsible for GSK-3β activation, among the miR-675-5p targets, thus indicating the molecular mediator through which miR-675-5p may control β-catenin nuclear localization. In conclusion, here we demonstrated that the inhibition of the hypoxia-induced non-coding RNA miR-675-5p hampered the nuclear localization of β-catenin by regulating GSK-3β activity, thus proposing the miR-675-5p as a new therapeutic target for the treatment of colorectal cancer.

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.

scholarly journals Blueberry Counteracts BV-2 Microglia Morphological and Functional Switch after LPS Challenge

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1830
Author(s):  
Maria Giovanna De Caris ◽  
Maddalena Grieco ◽  
Elisa Maggi ◽  
Antonio Francioso ◽  
Federica Armeli ◽  
...  
Keyword(s):  
Innate Immune ◽  
Cytoskeletal Organization ◽  
Cytoskeleton Organization ◽  
Lps Challenge ◽  
Migratory Capacity ◽  
M1 Polarization ◽  
Rac1 Activity ◽  
Tnf Α ◽  
Actin Cytoskeleton Organization ◽  
Pro Inflammatory Cytokines

Microglia, the innate immune cells of the CNS, respond to brain injury by activating and modifying their morphology. Our study arises from the great interest that has been focused on blueberry (BB) for the antioxidant and pharmacological properties displayed by its components. We analyzed the influence of hydroalcoholic BB extract in resting or lipopolysaccharide (LPS)-stimulated microglia BV-2 cells. BB exerted a protective effect against LPS-induced cytotoxicity, as indicated by cell viability. BB was also able to influence the actin cytoskeleton organization, to recover the control phenotype after LPS insult, and also to reduce LPS-driven migration. We evaluated the activity of Rho and Rac1 GTPases, which regulate both actin cytoskeletal organization and migratory capacity. LPS caused an increase in Rac1 activity, which was counteracted by BB extract. Furthermore, we demonstrated that, in the presence of BB, mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α decreased, as did the immunofluorescence signal of iNOS, whereas that of Arg-1 was increased. Taken together, our results show that, during the inflammatory response, BB extract shifts the M1 polarization towards the M2 phenotype through an actin cytoskeletal rearrangement. Based on that, we might consider BB as a nutraceutical with anti-inflammatory activities.

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 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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