Loss of MYO5B expression deregulates late endosome size which hinders mitotic spindle orientation

dc.contributor
[Leng C, Overeem AW, Li Q, Klappe K, Kuipers K] Department of Biomedical Sciences of Cells and Systems, section Molecular Cell Biology, University Medical Center Groningen, Groningen, the Netherlands. University of Groningen, Groningen, the Netherlands. [Cartón-Garcia F, Arango D] Investigació Biomèdica en Tumors de l'Aparell Digestiu, CIBBIM-Nanomedicine, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Leng, Changsen
dc.contributor.author
Carton García, Fernando
dc.contributor.author
Li, Qinghong
dc.contributor.author
Klappe, Karin
dc.contributor.author
Kuipers, Jeroen
dc.contributor.author
Arango Corro, Diego
dc.contributor.author
Overeem, Arend W.
dc.date.accessioned
2025-10-25T08:53:59Z
dc.date.available
2025-10-25T08:53:59Z
dc.date.issued
2020-09-07T11:33:08Z
dc.date.issued
2020-09-07T11:33:08Z
dc.date.issued
2019-11-04
dc.identifier
Leng C, Overeem AW, Cartón-Garcia F, Li Q, Klappe K, Kuipers J, et al. Loss of MYO5B expression deregulates late endosome size which hinders mitotic spindle orientation. PLoS Biol. 2019 Nov 4;17(11):e3000531.
dc.identifier
1544-9173
dc.identifier
https://hdl.handle.net/11351/5222
dc.identifier
10.1371/journal.pbio.3000531
dc.identifier
31682603
dc.identifier
000501223700025
dc.identifier.uri
http://hdl.handle.net/11351/5222
dc.description.abstract
MYO5B; Epithelial architecture; Recycling endosomes
dc.description.abstract
MYO5B; Arquitectura epitelial; Reciclaje de endosomas
dc.description.abstract
MYO5B; Arquitectura epitelial; Reciclatge d'endosomes
dc.description.abstract
Recycling endosomes regulate plasma membrane recycling. Recently, recycling endosome–associated proteins have been implicated in the positioning and orientation of the mitotic spindle and cytokinesis. Loss of MYO5B, encoding the recycling endosome–associated myosin Vb, is associated with tumor development and tissue architecture defects in the gastrointestinal tract. Whether loss of MYO5B expression affects mitosis is not known. Here, we demonstrate that loss of MYO5B expression delayed cytokinesis, perturbed mitotic spindle orientation, led to the misorientation of the plane of cell division during the course of mitosis, and resulted in the delamination of epithelial cells. Remarkably, the effects on spindle orientation, but not cytokinesis, were a direct consequence of physical hindrance by giant late endosomes, which were formed in a chloride channel–sensitive manner concomitant with a redistribution of chloride channels from the cell periphery to late endosomes upon loss of MYO5B. Rab7 availability was identified as a limiting factor for the development of giant late endosomes. In accordance, increasing rab7 availability corrected mitotic spindle misorientation and cell delamination in cells lacking MYO5B expression. In conclusion, we identified a novel role for MYO5B in the regulation of late endosome size control and identify the inability to control late endosome size as an unexpected novel mechanism underlying defects in cell division orientation and epithelial architecture.
dc.description.abstract
AD: Association for International Cancer Research (AICR13-0245), https://www.aicr.org AD: European Regional Development Fund (ERDF; PI16/00540 and AC15/00066), https://ec.europa.eu/regional_policy/en/funding/erdf AD: Spanish Association Against Cancer (AECC GCA15152966ARAN), https://www.uicc.org AD: the Instituto de Salud Carlos III, https://www.isciii.es/Paginas/Inicio.aspx IZ: The Dutch Research Council, Domain Applied and Engineering Sciences, https://www.nwo.nl/en JK: The Netherlands Organisation for Health Research and Development, 91111.006, https://www.zonmw.nl/en/ JK: The Dutch Research Council, 175-010-2009-023, https://www.nwo.nl/en CK: Chinese Scholarship Council, https://www.chinesescholarshipcouncil.com/ QL: Chinese Scholarship Council, https://www.chinesescholarshipcouncil.com/ YC: Chinese Scholarship Council, https://www.chinesescholarshipcouncil.com/
dc.format
application/pdf
dc.format
application/pdf
dc.format
application/pdf
dc.format
application/mp4
dc.format
application/mp4
dc.format
application/mp4
dc.format
application/mp4
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application/mp4
dc.format
application/mp4
dc.language
eng
dc.publisher
Public Library of Science
dc.relation
PloS Biology;17(11)
dc.relation
https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000531
dc.relation
info:eu-repo/grantAgreement/ES/PE2013-2016/PI16%2F00540
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.source
Scientia
dc.subject
Orgànuls cel·lulars
dc.subject
Miosina
dc.subject
Cèl·lules - Divisió
dc.subject
ANATOMY::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Cytoplasmic Vesicles::Transport Vesicles::Endosomes
dc.subject
CHEMICALS AND DRUGS::Enzymes and Coenzymes::Enzymes::Hydrolases::Acid Anhydride Hydrolases::Adenosine Triphosphatases::Molecular Motor Proteins::Myosins::Myosin Heavy Chains
dc.subject
PHENOMENA AND PROCESSES::Genetic Phenomena::Cell Division
dc.subject
ANATOMÍA::células::estructuras celulares::espacio intracelular::citoplasma::estructuras citoplasmáticas::orgánulos::vesículas citoplasmáticas::vesículas transportadoras::endosomas
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::enzimas y coenzimas::enzimas::hidrolasas::ácido anhídrido hidrolasas::adenosina trifosfatasas::proteínas motoras moleculares::miosinas::cadenas pesadas de la miosina
dc.subject
FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::ciclo celular::división celular
dc.title
Loss of MYO5B expression deregulates late endosome size which hinders mitotic spindle orientation
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion


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