Microtubule Acetylation Is Required for Mechanosensation in Drosophila

Yan, Connie; Wang, Fei; Peng, Yun; Williams, Claire; Jenkins, Brian V.; Wildonger, Jill; Kim, Hyeonjin; Perr, Jonathan B.; Vaughan, Joshua C.; Kern, Megan E.; Falvo, Michael R.; O’Brien, E. Timothy; Superfine, Richard; Tuthill, John C.; Xiang, Yang; Rogers, Stephen L.; Parrish, Jay Z.

doi:10.1016/j.celrep.2018.09.075

Cited by 63 publications

(71 citation statements)

References 76 publications

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“…2 H). These results align with reports that acetylMTs are responsible for the mechanosensitive touch response in mice and Drosophila 14,21 as well as evidence that acetylated α-tubulin underlies the increased resistance seen with repetitive strain to microtubules in vitro 22,23 ; a property that would facilitate the transfer of energy for mechanotransduction in striated muscle 4,8,20 .…”

Section: Resultssupporting

confidence: 90%

Tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle

Coleman

Joca

Shi

et al. 2020

Preprint

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Microtubules tune cytoskeletal stiffness to regulate the mechanics and mechanotransduction of striated muscle. While recent evidence suggests that microtubules enriched in detyrosinated α-tubulin are responsible for these effects in healthy muscle, and for their excess in disease, the possible contribution from several other α-tubulin modifications has not been investigated. Here we used genetic or pharmacologic strategies in isolated cardiomyocytes or skeletal myofibers to increase the level of acetylated α -tubulin without altering the level of detyrosinated α -tubulin. We show that microtubules enriched in acetylated α-tubulin contribute to the cytoskeletal stiffness and viscoelastic resistance, showing slowed rates of contraction and relaxation during unloaded contraction, and increased activation of NADPH Oxidase 2 (Nox2) by mechanotransduction. Together these findings add to growing evidence that microtubules contribute to the mechanobiology of striated muscle in health and disease.

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Section: Resultssupporting

confidence: 90%

Tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle

Coleman

Joca

Shi

et al. 2020

Preprint

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“…Acetylation is a prominent tubulin PTM in neurons, however its absence in aTAT-knockout mice induced surprisingly mild neurological defects 151 , the most remarkable being the loss of touch sensation 215 . This mirrors touch-sensation defects in acetylation-defective Drosophila 216 , as well as in C. elegans, where aTAT1 (Mec-17)-mediated acetylation 217 is important for the formation of the characteristic 15-protofilament microtubules 85 that are essential for touch sensation 218 . Mutation of K40 in the major neuronal α-tubulin isotype in 20 Drosophila (αTub84B) further highlighted the importance of acetylation in dendritic refinement of sensory neurons .…”

Section: 2) Functions Of Tubulin Ptms In Neuronsmentioning

confidence: 75%

The tubulin code and its role in controlling microtubule properties and functions

Janke

Magiera

2020

Nat Rev Mol Cell Biol

611

519

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Microtubules are core components of the eukaryotic cytoskeleton with essential roles in cell division, shaping, intracellular transport, and motility. Despite their functional heterogeneity, microtubules have a highly conserved structure made from almost identical molecular building blocks; the tubulin proteins. Alternative tubulin isotypes and a variety of posttranslational modifications control the properties and functions of the microtubule cytoskeleton, a concept known as the 'tubulin code'. This concept first emerged with the discovery that α-and β-tubulin are each encoded by multiple genes, but it took decades before its functional importance begun to emerge. Here we review the current understanding of the molecular components of the tubulin code, and how they impact microtubule properties and functions. We discuss how tubulin isotypes and posttranslational modifications control microtubule behaviour at the molecular level, and how this translates into physiological functions at the cellular and organism levels. We further show how the fine-tuning of microtubule functions by some tubulin modifications affects homeostasis, and how its perturbation can lead to a large variety of dysfunctions, many of them linked to human disorders.

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“…KIF2A is a member of the kinesin-13 family of proteins, and serves the function of depolymerizing the ends of microtubules (MTs) (24,25). MTs are vital components of the cytoskeleton and are involved in the invasion and metastasis of cancer (26,27). Therefore, the aim of the present study was to evaluate the expression of KIF2A in NPC and explore the relationship between KIF2A expression and the basic characteristics of 5-8F cells.…”

Section: Discussionmentioning

confidence: 99%

Effects of KIF2A on the prognosis of nasopharyngeal carcinoma and nasopharyngeal carcinoma cells

Zhang

Liu

et al. 2019

Oncol Lett

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Nasopharyngeal carcinoma (NPC) is a common tumor in south China. Kinesin family member 2A (KIF2A) belongs to the kinesin-13 family and is associated with the growth and invasion of a number of different types of human cancer, including ovarian, breast and prostate cancer. The aim of the present study was to evaluate the expression of KIF2A in NPC and explore the relationship between KIF2A and the basic characteristics of 5-8F cells. Immunohistochemistry was performed on tissues from 97 patients with NPC to assess KIF2A protein expression. KIF2A was knocked down by a specific short interfering (si)RNA in 5-8F cell lines. Cell proliferation, apoptosis and cycle were analyzed by MTT assay and flow cytometry. The invasive ability and angiogenesis were evaluated by Matrigel assay and reverse transcription-quantitative PCR. The level of KIF2A was associated with the growth and migration of primary tumor, nodal status and tumor stage. The viability of KIF2A-knockdown cells was decreased compared with that of the control cells. The number of apoptotic cells, as well as the percentage of cells in the G0/G1 phase, was higher in the KIF2A siRNA group compared with the control group. The invasive and angiogenetic ability of 5-8F cells in the KIF2A siRNA group was decreased compared with the control group. In conclusion, the expression of KIF2A correlated with the poor clinicopathological features in NPC. Therefore, KIF2A may serve an important role in the progression of NPC and proliferation of 5-8F cells, which might present a potential therapeutic target for patients with NPC.

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Microtubule Acetylation Is Required for Mechanosensation in Drosophila

Cited by 63 publications

References 76 publications

Tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle

Tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle

The tubulin code and its role in controlling microtubule properties and functions

Effects of KIF2A on the prognosis of nasopharyngeal carcinoma and nasopharyngeal carcinoma cells

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