02652nas a2200277   4500008004100000245011100041210006900152260000900221300000700230490000700237520177100244653001002015653001702025653001002042653001602052653002202068653002002090653001202110653001402122653000802136653001602144100002802160700002902188700003602217856012102253       2021                        eng d00aExtracellular HDAC6 ZnF UBP domain modulates the actin network and post-translational modifications of Tau0 aExtracellular HDAC6 ZnF UBP domain modulates the actin network a  cMAY   a490 v193 a<p>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-3 beta 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-3 beta increases without any change in total GSK-3 beta 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.</p>10aActin10aCytoskeleton10aHDAC610aMicrotubule10aneurodegeneration10aPhosphorylation10aPodonut10aPodosomes10aTau10aTauopathies1 aBalmik, Abhishek, Ankur1 aSonawane, Shweta, Kishor1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/extracellular-hdac6-znf-ubp-domain-modulates-actin-network-and-post-translational