Tubulin Acetylation Alone Does Not Affect Kinesin-1 Velocity and Run Length In Vitro

Walter, Wilhelm J.; Beránek, Václav; Fischermeier, Elisabeth; Diez, Stefan

doi:10.1371/journal.pone.0042218

Cited by 90 publications

(100 citation statements)

References 28 publications

(36 reference statements)

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“…Acetylated microtubules are generally thought to be more stable than unmodified microtubules, but no direct evidence has shown that acetylation modification of microtubules directly influences tubulin polymerization or depolymerization kinetics in vitro (18). In addition, no clear differences in microtubule structure or tubulin conformation have been found between electron cryomicroscopy reconstructions of maximally deacetylated or acetylated microtubules (19), and the levels at which kinesin-1 binds to acetylated microtubules and deacetylated microtubules are similar (20,21). These findings require further investigation into the mechanism by which acetylation of ␣-tubulin enhances the fusion of IBs of HPIV3 via interaction with the N-P complex.…”

Section: Discussionmentioning

confidence: 99%

Inclusion Body Fusion of Human Parainfluenza Virus Type 3 Regulated by Acetylated α-Tubulin Enhances Viral Replication

Zhang

Jiang

Cheng

et al. 2017

J Virol

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Viral inclusion bodies (IBs), or replication factories, are unique structures generated by viral proteins together with some cellular proteins as a platform for efficient viral replication, but little is known about the mechanism underlying IB formation and fusion. Our previous study demonstrated that the interaction between the nucleoprotein (N) and phosphoprotein (P) of human parainfluenza virus type 3 (HPIV3), an enveloped virus with great medical impact, can form IBs. In this study, we found that small IBs can fuse with each other to form large IBs that enhance viral replication. Furthermore, we found that acetylated ␣-tubulin interacts with the N-P complex and colocalizes with IBs of HPIV3 but does not interact with the N-P complex of human respiratory syncytial virus or vesicular stomatitis virus and does not colocalize with IBs of human respiratory syncytial virus. Most importantly, enhancement of ␣-tubulin acetylation using the pharmacological inhibitor trichostatin A (TSA), RNA interference (RNAi) knockdown of the deacetylase enzymes histone deacetylase 6 (HDAC6) and sirtuin 2 (SIRT2), or expression of ␣-tubulin acetyltransferase 1 (␣-TAT1) resulted in the fusion of small IBs into large IBs and effective viral replication. In contrast, suppression of acetylation of ␣-tubulin by overexpressing HDAC6 and SIRT2 profoundly inhibited the fusion of small IBs and viral replication. Our findings offer previously unidentified mechanistic insights into the regulation of viral IB fusion by acetylated ␣-tubulin, which is critical for viral replication.IMPORTANCE Inclusion bodies (IBs) are unique structures generated by viral proteins and some cellular proteins as a platform for efficient viral replication. Human parainfluenza virus type 3 (HPIV3) is a nonsegmented single-stranded RNA virus that mainly causes lower respiratory tract disease in infants and young children. However, no vaccines or antiviral drugs for HPIV3 are available. Therefore, understanding virus-host interactions and developing new antiviral strategies are increasingly important. Acetylation on lysine (K) 40 of ␣-tubulin is an evolutionarily conserved modification and plays an important role in many cellular processes, but its role in viral IB dynamics has not been fully explored. To our knowledge, our findings are the first to show that acetylated ␣-tubulin enhances viral replication by regulating HPIV3 IB fusion.KEYWORDS inclusion bodies, human parainfluenza virus type 3, acetylated ␣-tubulin H uman parainfluenza virus type 3 (HPIV3) is a nonsegmented single-stranded RNA virus (NSV) that belongs to the Paramyxoviridae family and mainly causes lower respiratory tract disease in infants and young children (1). However, no vaccines are available for HPIV3, and therefore, a deeper understanding of the replication of HPIV3

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Section: Discussionmentioning

confidence: 99%

Inclusion Body Fusion of Human Parainfluenza Virus Type 3 Regulated by Acetylated α-Tubulin Enhances Viral Replication

Zhang

Jiang

Cheng

et al. 2017

J Virol

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“…However, a direct regulation of kinesin-1 motility by K40 acetylation of tubulin has not been confirmed in vitro (Kaul et al, 2014;Walter et al, 2012), suggesting that other mechanisms contribute to the transport phenotype observed in cells.…”

Section: Molecular Mechanisms Controlled By Tubulin Ptmsmentioning

confidence: 97%

The tubulin code at a glance

Gadadhar

Bodakuntla

Natarajan

et al. 2017

Journal of Cell Science

217

227

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Microtubules are key cytoskeletal elements of all eukaryotic cells and are assembled of evolutionarily conserved α-tubulin-β-tubulin heterodimers. Despite their uniform structure, microtubules fulfill a large diversity of functions. A regulatory mechanism to control the specialization of the microtubule cytoskeleton is the 'tubulin code', which is generated by (i) expression of different α-and β-tubulin isotypes, and by (ii) post-translational modifications of tubulin. In this Cell Science at a Glance article and the accompanying poster, we provide a comprehensive overview of the molecular components of the tubulin code, and discuss the mechanisms by which these components contribute to the generation of functionally specialized microtubules.

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“…A consecutive change in MT conformation might therefore enhance motor recruitment to MTs (Dompierre et al, 2007;Hammond et al, 2009;Reed et al, 2006). Conversely, the role of tubulin acetylation upon molecular motor recruitment and function has been questioned in motility assays using tubulin acetylated in vitro (Soppina et al, 2012;Walter et al, 2012). These studies proposed that the recruitment of kinesin-1 to acetylated MTs and its velocity were not affected, but other tubulin modifications (de-tyrosination and polyglutamylation) could have masked the effect of acetylation.…”

Section: Autophagy and Microtubules 1075mentioning

confidence: 99%

Autophagy and microtubules – new story, old players

Mackeh

Perdiz

Lorin

et al. 2013

Journal of Cell Science

189

181

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SummaryBoth at a basal level and after induction (especially in response to nutrient starvation), the function of autophagy is to allow cells to degrade and recycle damaged organelles, proteins and other biological constituents. Here, we focus on the role microtubules have in autophagosome formation, autophagosome transport across the cytoplasm and in the formation of autolysosomes. Recent insights into the exact relationship between autophagy and microtubules now point to the importance of microtubule dynamics, tubulin posttranslational modifications and microtubule motors in the autophagy process. Such factors regulate signaling pathways that converge to stimulate autophagosome formation. They also orchestrate the movements of pre-autophagosomal structures and autophagosomes or more globally organize and localize immature and mature autophagosomes and lysosomes. Most of the factors that now appear to link microtubules to autophagosome formation or to autophagosome dynamics and fate were identified initially without the notion that sequestration, recruitment and/or interaction with microtubules contribute to their function. Spatial and temporal coordination of many stages in the life of autophagosomes thus underlines the integrative role of microtubules and progressively reveals hidden parts of the autophagy machinery.

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Tubulin Acetylation Alone Does Not Affect Kinesin-1 Velocity and Run Length In Vitro

Cited by 90 publications

References 28 publications

Inclusion Body Fusion of Human Parainfluenza Virus Type 3 Regulated by Acetylated α-Tubulin Enhances Viral Replication

Inclusion Body Fusion of Human Parainfluenza Virus Type 3 Regulated by Acetylated α-Tubulin Enhances Viral Replication

The tubulin code at a glance

Autophagy and microtubules – new story, old players

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