1. Academic Validation
  2. Microtubule polyglutamylation and acetylation drive microtubule dynamics critical for platelet formation

Microtubule polyglutamylation and acetylation drive microtubule dynamics critical for platelet formation

  • BMC Biol. 2018 Oct 18;16(1):116. doi: 10.1186/s12915-018-0584-6.
Juliette van Dijk 1 2 Guillaume Bompard 1 3 Julien Cau 1 3 4 Shinji Kunishima 5 6 Gabriel Rabeharivelo 1 2 Julio Mateos-Langerak 1 3 4 Chantal Cazevieille 1 7 Patricia Cavelier 1 8 Brigitte Boizet-Bonhoure 1 3 Claude Delsert 1 2 9 Nathalie Morin 10 11
Affiliations

Affiliations

  • 1 Universités de Montpellier, 34293, Montpellier, France.
  • 2 CRBM, CNRS, UMR 5237, 1919 Route de Mende, 34293, Montpellier, France.
  • 3 IGH, CNRS UMR9002, 141, rue de la Cardonille, 34396, Montpellier, France.
  • 4 Montpellier Rio Imaging, 34293, Montpellier, France.
  • 5 Department of Advanced Diagnosis, National Hospital Organization Nagoya Medical Center, 4-1-1 Sannomaru, Naka-ku, Nagoya, 4600001, Japan.
  • 6 Present address: Department of Medical Technology, Gifu University of Medical Science, Seki, Gifu, 5013892, Japan.
  • 7 INM, INSERM UMR1051, 34293, Montpellier, France.
  • 8 IGMM, CNRS, UMR 5535, 1919 Route de Mende, 34293, Montpellier, France.
  • 9 3AS Station Expérimentale d'Aquaculture Ifremer, Chemin de Maguelone, 34250, Palavas-les-Flots, France.
  • 10 Universités de Montpellier, 34293, Montpellier, France. nathalie.morin@crbm.cnrs.fr.
  • 11 CRBM, CNRS, UMR 5237, 1919 Route de Mende, 34293, Montpellier, France. nathalie.morin@crbm.cnrs.fr.
Abstract

Background: Upon maturation in the bone marrow, polyploid megakaryocytes elongate very long and thin cytoplasmic branches called proplatelets. Proplatelets enter the sinusoids blood vessels in which platelets are ultimately released. Microtubule dynamics, bundling, sliding, and coiling, drive these dramatic morphological changes whose regulation remains poorly understood. Microtubule properties are defined by tubulin isotype composition and post-translational modification patterns. It remains unknown whether microtubule post-translational modifications occur in proplatelets and if so, whether they contribute to platelet formation.

Results: Here, we show that in proplatelets from mouse megakaryocytes, microtubules are both acetylated and polyglutamylated. To bypass the difficulties of working with differentiating megakaryocytes, we used a cell model that allowed us to test the functions of these modifications. First, we show that α2bβ3integrin signaling in D723H cells is sufficient to induce β1tubulin expression and recapitulate the specific microtubule behaviors observed during proplatelet elongation and platelet release. Using this model, we found that microtubule acetylation and polyglutamylation occur with different spatio-temporal patterns. We demonstrate that microtubule acetylation, polyglutamylation, and β1tubulin expression are mandatory for proplatelet-like elongation, swelling formation, and cytoplast severing. We discuss the functional importance of polyglutamylation of β1tubulin-containing microtubules for their efficient bundling and coiling during platelet formation.

Conclusions: We characterized and validated a powerful cell model to address microtubule behavior in mature megakaryocytes, which allowed us to demonstrate the functional importance of microtubule acetylation and polyglutamylation for platelet release. Furthermore, we bring evidence of a link between the expression of a specific tubulin isotype, the occurrence of microtubule post-translational modifications, and the acquisition of specific microtubule behaviors. Thus, our findings could widen the current view of the regulation of microtubule behavior in cells such as osteoclasts, spermatozoa, and neurons, which express distinct tubulin isotypes and display specific microtubule activities during differentiation.

Keywords

Acetylation; CHO cells; Megakaryocytes; Microtubules; Platelets; Polyglutamylation; Tubulin isotype; αIIbβ3 integrin.

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