Marginal band microtubules are acetylated by αTAT1

Abstract

The discoid shape of resting platelets is maintained by a peripheral, circular bundle of microtubules called marginal band. Marginal band microtubules are acetylated on lysine 40 of the alpha-tubulin subunits. We have previously shown that the deacetylase HDAC6 is responsible for tubulin deacetylation in platelets and that the hyperacetylated state of the microtubules in HDAC6KO platelets correlates with faster activation/spreading kinetics, pointing to a regulatory role of this modification. So far, the question about the reverse enzyme, responsible for tubulin acetylation in platelets, has remained unanswered. Several enzymes have been described as having tubulin acetylation activity. Here we identify αTAT1 as the enzyme responsible for the acetylation of marginal band microtubules. We show that αTAT1 deficiency has only minor consequences for platelet production and function. A residual tubulin acetylation level in αTAT1 deficient platelet lysates suggests the presence of an additional tubulin-acetylating enzyme that is unable to acetylate marginal band microtubules.

Keywords:

• Acetylation
• acetyltransferase
• microtubules
• post-translational modification
• tubulin

Acknowledgements

We are grateful to Paul Heppenstall for providing the αTAT1KO mice and Patrick Matthias for the HDAC6KO mice. We thank Thérèse Rossini for platelet count determination.

Author contributions

A.-S.R., M.B., C.R., T.B., S.M., K.S. performed experiments. E.B.-F. was implicated in data analysis. F.L. and K.S. designed experiments and wrote the paper. S.K. and L.L. financially contributed to the study. All authors interpreted results and reviewed the manuscript.

Disclosure statement

The authors have no declaration of interest to disclose.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This work was supported by the Fondation Recherche Médicale (FRM, grant number DEI20151234416) and the University Grenoble Alpes (UGA, grant number AGIR-POLE FRAG15CS08) as well as by funds from the Association de Recherche et Développement en Médecine et Santé Publique (ARMESA to M.B.).