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| Van Dijk, Juliette; Bompard, Guillaume; Rabeharivelo, Gabriel; Cau, Julien; Delsert, Claude; Morin, Nathalie. |
| 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... |
| Tipo: Text |
Palavras-chave: Microtubules; Acetylation; Megakaryocytes; Proplatelet; P21-activated kinase 1 PAK1; Acetyltransferase MEC-17. |
| Ano: 2020 |
URL: https://archimer.ifremer.fr/doc/00654/76594/77743.pdf |
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| Bompard, Guillaume; Rabeharivelo, Gabriel; Frank, Marie; Cau, Julien; Delsert, Claude; Morin, Nathalie. |
| Ran is an essential GTPase that controls nucleocytoplasmic transport, mitosis, and nuclear envelope formation. These functions are regulated by interaction of Ran with different partners, and by formation of a Ran-GTP gradient emanating from chromatin. Here, we identify a novel level of Ran regulation. We show that Ran is a substrate for p21-activated kinase 4 (PAK4) and that its phosphorylation on serine-135 increases during mitosis. The endogenous phosphorylated Ran and active PAK4 dynamically associate with different components of the microtubule spindle during mitotic progression. A GDP-ound Ran phosphomimetic mutant cannot undergo RCC1-mediated GDP/GTP exchange and cannot induce microtubule asters in mitotic Xenopus egg extracts. Conversely,... |
| Tipo: Text |
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| Ano: 2010 |
URL: http://archimer.ifremer.fr/doc/00014/12502/9353.pdf |
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| Van Dijk, Juliette; Bompard, Guillaume; Cau, Julien; Kunishima, Shinji; Rabeharivelo, Gabriel; Mateos-langerak, Julio; Cazevieille, Chantal; Cavelier, Patricia; Boizet-bonhoure, Brigitte; Delsert, Claude; Morin, Nathalie. |
| 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... |
| Tipo: Text |
Palavras-chave: Microtubules; Acetylation; Polyglutamylation; Tubulin isotype; Platelets; Megakaryocytes; IIb3 integrin; CHO cells. |
| Ano: 2018 |
URL: https://archimer.ifremer.fr/doc/00463/57463/59577.pdf |
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