Please use this identifier to cite or link to this item: https://doi.org/10.1242/jcs.03431
Title: HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions
Authors: Tran, A.D.-A
Marmo, T.P
Salam, A.A
Che, S
Finkelstein, E
Kabarriti, R
Xenias, H.S
Mazitschek, R
Hubbert, C
Kawaguchi, Y
Sheetz, M.P 
Yao, T.-P
Bulinski, J.C
Keywords: alpha tubulin
histone deacetylase 6
histone deacetylase inhibitor
tubacin
unclassified drug
animal cell
animal tissue
article
bleaching
cell adhesion
cell migration
cell motility
cell spreading
controlled study
cytoskeleton
deacetylation
enzyme activity
enzyme inhibition
focal adhesion
microtubule
nonhuman
priority journal
Acetylation
Animals
Cell Adhesion
Cell Movement
Cercopithecus aethiops
COS Cells
Histone Deacetylases
Humans
Tubulin
Issue Date: 2007
Citation: Tran, A.D.-A, Marmo, T.P, Salam, A.A, Che, S, Finkelstein, E, Kabarriti, R, Xenias, H.S, Mazitschek, R, Hubbert, C, Kawaguchi, Y, Sheetz, M.P, Yao, T.-P, Bulinski, J.C (2007). HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions. Journal of Cell Science 120 (8) : 1469-1479. ScholarBank@NUS Repository. https://doi.org/10.1242/jcs.03431
Rights: Attribution 4.0 International
Abstract: Genetic or pharmacological alteration of the activity of the histone deacetylase 6 (HDAC6) induces a parallel alteration in cell migration. Using tubacin to block deacetylation of ?-tubulin, and not other HDAC6 substrates, yielded a motility reduction equivalent to agents that block all NAD-independent HDACs. Accordingly, we investigated how the failure to deacetylate tubulin contributes to decreased motility in HDAC6-inhibited cells. Testing the hypothesis that motility is reduced because cellular adhesion is altered, we found that inhibiting HDAC6 activity towards tubulin rapidly increased total adhesion area. Next, we investigated the mechanism of the adhesion area increase. Formation of adhesions proceeded normally and cell spreading was more rapid in the absence of active HDAC6; however, photobleaching assays and adhesion breakdown showed that adhesion turnover was slower. To test the role of hyperacetylated tubulin in altering adhesion turnover, we measured microtubule dynamics in HDAC6-inhibited cells because dynamic microtubules are required to target adhesions for turnover. HDAC6 inhibition yielded a decrease in microtubule, dynamics that was sufficient to decrease focal adhesion turnover. Thus, our results suggest a scenario in which the decreased dynamics of hyperacetylated microtubules in HDAC6-inhibited cells compromises their capacity to mediate the focal adhesion dynamics required for rapid cell migration.
Source Title: Journal of Cell Science
URI: https://scholarbank.nus.edu.sg/handle/10635/181040
ISSN: 0021-9533
DOI: 10.1242/jcs.03431
Rights: Attribution 4.0 International
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