PAK1 Regulates MEC-17 Acetyltransferase Activity and Microtubule Acetylation during Proplatelet Extension

Type Article
Date 2020-10
Language English
Author(s) Van Dijk Juliette1, 2, Bompard Guillaume1, 2, Rabeharivelo Gabriel1, 2, Cau Julien1, 3, 4, Delsert Claude1, 2, 5, Morin Nathalie1, 2
Affiliation(s) 1 : Université de Montpellier, 34293 Montpellier, France
2 : CRBM, CNRS, UMR 5237, 1919 Route de Mende, 34293 Montpellier, France
3 : IGH, CNRS UMR 9002, 141, Rue de la Cardonille, 34396 Montpellier, France
4 : Montpellier Rio Imaging, 34293 Montpellier, France
5 : Station Expérimentale d’Aquaculture Ifremer, Chemin de Maguelone, 34250 Palavas-les-Flots, France
Source International Journal Of Molecular Sciences (1422-0067) (MDPI AG), 2020-10 , Vol. 21 , N. 20 , P. 7531 (17p.)
DOI 10.3390/ijms21207531
WOS© Times Cited 4
Note This article belongs to the Special Issue Molecular Research on Platelet Activity in Health and Disease 2.0
Keyword(s) microtubules, acetylation, megakaryocytes, proplatelet, p21-activated kinase 1 PAK1, acetyltransferase MEC-17

Mature megakaryocytes extend long processes called proplatelets from which platelets are released in the blood stream. The Rho GTPases Cdc42 and Rac as well as their downstream target, p21-activated kinase 2 (PAK2), have been demonstrated to be important for platelet formation. Here we address the role, during platelet formation, of PAK1, another target of the Rho GTPases. PAK1 decorates the bundled microtubules (MTs) of megakaryocyte proplatelets. Using a validated cell model which recapitulates proplatelet formation, elongation and platelet release, we show that lack of PAK1 activity increases the number of proplatelets but restrains their elongation. Moreover, in the absence of PAK1 activity, cells have hyperacetylated MTs and lose their MT network integrity. Using inhibitors of the tubulin deacetylase HDAC6, we demonstrate that abnormally high levels of MT acetylation are not sufficient to increase the number of proplatelets but cause loss of MT integrity. Taken together with our previous demonstration that MT acetylation is required for proplatelet formation, our data reveal that MT acetylation levels need to be tightly regulated during proplatelet formation. We identify PAK1 as a direct regulator of the MT acetylation levels during this process as we found that PAK1 phosphorylates the MT acetyltransferase MEC-17 and inhibits its activity.

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Van Dijk Juliette, Bompard Guillaume, Rabeharivelo Gabriel, Cau Julien, Delsert Claude, Morin Nathalie (2020). PAK1 Regulates MEC-17 Acetyltransferase Activity and Microtubule Acetylation during Proplatelet Extension. International Journal Of Molecular Sciences, 21(20), 7531 (17p.). Publisher's official version : , Open Access version :