Microtubule polyglutamylation and acetylation drive microtubule dynamics critical for platelet formation
|Author(s)||Van Dijk Juliette1, 2, Bompard Guillaume1, 3, Cau Julien1, 3, 4, Kunishima Shinji5, 6, Rabeharivelo Gabriel1, 2, Mateos-Langerak Julio1, 3, 4, Cazevieille Chantal1, 7, Cavelier Patricia1, 8, Boizet-Bonhoure Brigitte1, 3, Delsert Claude1, 2, 9, Morin Nathalie1, 2|
|Affiliation(s)||1 : Univ Montpellier, F-34293 Montpellier, France.
2 : CNRS, UMR 5237, CRBM, 1919 Route Mende, F-34293 Montpellier, France.
3 : CNRS, UMR9002, IGH, 141 Rue Cardonille, F-34396 Montpellier, France.
4 : Montpellier Rio Imaging, F-34293 Montpellier, France.
5 : Natl Hosp Org Nagoya Med Ctr, Dept Adv Diag, Naka Ku, 4-1-1 Sannomaru, Nagoya, Aichi 4600001, Japan.
6 : Gifu Univ Med Sci, Dept Med Technol, Gifu 5013892, Japan.
7 : INSERM, UMR1051, INM, F-34293 Montpellier, France.
8 : CNRS, UMR 5535, IGMM, 1919 Route Mende, F-34293 Montpellier, France.
9 : IFREMER, Stn Expt Aquaculture 3AS, Chemin Maguelone, F-34250 Palavas Les Flots, France.
|Source||Bmc Biology (1741-7007) (Bmc), 2018-10 , Vol. 16 , N. 1 , P. 116 (17p.)|
|Keyword(s)||Microtubules, Acetylation, Polyglutamylation, Tubulin isotype, Platelets, Megakaryocytes, IIb3 integrin, CHO cells|
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.
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.
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.