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Microtubule plus-end tracking Adenopolyposis Coli negatively regulates proplatelet formation
Platelets are produced upon profound reorganization of mature megakaryocytes (MK) leading to proplatelet elongation and release into the blood stream, a process termed thrombopoiesis. This highly dynamic process requires microtubules (MT) reorganization by mechanisms that are still incompletely unde...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202313/ https://www.ncbi.nlm.nih.gov/pubmed/30361531 http://dx.doi.org/10.1038/s41598-018-34118-y |
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author | Strassel, C. Moog, S. Mallo, L. Eckly, A. Freund, M. Gachet, C. Lanza, F. |
author_facet | Strassel, C. Moog, S. Mallo, L. Eckly, A. Freund, M. Gachet, C. Lanza, F. |
author_sort | Strassel, C. |
collection | PubMed |
description | Platelets are produced upon profound reorganization of mature megakaryocytes (MK) leading to proplatelet elongation and release into the blood stream, a process termed thrombopoiesis. This highly dynamic process requires microtubules (MT) reorganization by mechanisms that are still incompletely understood. Adenomatous polyposis coli (APC) is a microtubule plus-end tracking protein involved in the regulation of MT in a number of cell systems and its inactivation has been reported to alter hematopoiesis. The aim of our study was to investigate the role of APC in megakaryopoiesis and the final steps of platelet formation. Down-regulation of APC in cultured human MK by RNA interference increased endomitosis and the proportion of cells able to extend proplatelets (68.8% (shAPC1) and 52.5% (shAPC2) vs 28.1% in the control). Similarly an increased ploidy and amplification of the proplatelet network were observed in MK differentiated from Lin- cells of mice with APC-deficiency in the MK lineage. In accordance, these mice exhibited increased platelet counts when compared to wild type mice (1,323 ± 111 vs 919 ± 52 platelets/µL; n = 12 p 0.0033**). Their platelets had a normal size, ultrastructure and number of microtubules coils and their main functions were also preserved. Loss of APC resulted in lower levels of acetylated tubulin and decreased activation of the Wnt signaling pathway. Thus, APC appears as an important regulator of proplatelet formation and overall thrombopoiesis. |
format | Online Article Text |
id | pubmed-6202313 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-62023132018-10-29 Microtubule plus-end tracking Adenopolyposis Coli negatively regulates proplatelet formation Strassel, C. Moog, S. Mallo, L. Eckly, A. Freund, M. Gachet, C. Lanza, F. Sci Rep Article Platelets are produced upon profound reorganization of mature megakaryocytes (MK) leading to proplatelet elongation and release into the blood stream, a process termed thrombopoiesis. This highly dynamic process requires microtubules (MT) reorganization by mechanisms that are still incompletely understood. Adenomatous polyposis coli (APC) is a microtubule plus-end tracking protein involved in the regulation of MT in a number of cell systems and its inactivation has been reported to alter hematopoiesis. The aim of our study was to investigate the role of APC in megakaryopoiesis and the final steps of platelet formation. Down-regulation of APC in cultured human MK by RNA interference increased endomitosis and the proportion of cells able to extend proplatelets (68.8% (shAPC1) and 52.5% (shAPC2) vs 28.1% in the control). Similarly an increased ploidy and amplification of the proplatelet network were observed in MK differentiated from Lin- cells of mice with APC-deficiency in the MK lineage. In accordance, these mice exhibited increased platelet counts when compared to wild type mice (1,323 ± 111 vs 919 ± 52 platelets/µL; n = 12 p 0.0033**). Their platelets had a normal size, ultrastructure and number of microtubules coils and their main functions were also preserved. Loss of APC resulted in lower levels of acetylated tubulin and decreased activation of the Wnt signaling pathway. Thus, APC appears as an important regulator of proplatelet formation and overall thrombopoiesis. Nature Publishing Group UK 2018-10-25 /pmc/articles/PMC6202313/ /pubmed/30361531 http://dx.doi.org/10.1038/s41598-018-34118-y Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Strassel, C. Moog, S. Mallo, L. Eckly, A. Freund, M. Gachet, C. Lanza, F. Microtubule plus-end tracking Adenopolyposis Coli negatively regulates proplatelet formation |
title | Microtubule plus-end tracking Adenopolyposis Coli negatively regulates proplatelet formation |
title_full | Microtubule plus-end tracking Adenopolyposis Coli negatively regulates proplatelet formation |
title_fullStr | Microtubule plus-end tracking Adenopolyposis Coli negatively regulates proplatelet formation |
title_full_unstemmed | Microtubule plus-end tracking Adenopolyposis Coli negatively regulates proplatelet formation |
title_short | Microtubule plus-end tracking Adenopolyposis Coli negatively regulates proplatelet formation |
title_sort | microtubule plus-end tracking adenopolyposis coli negatively regulates proplatelet formation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202313/ https://www.ncbi.nlm.nih.gov/pubmed/30361531 http://dx.doi.org/10.1038/s41598-018-34118-y |
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