dc.creator | Oropesa-Avila, M. | es |
dc.creator | Fernandez-Vega, A. | es |
dc.creator | Mata Fernández, María de la | es |
dc.creator | Maraver, J. G. | es |
dc.creator | Cordero, Mario D. | es |
dc.creator | Cotán, D. | es |
dc.creator | Miguel Rodríguez, Manuel de | es |
dc.creator | Sánchez-Alcázar, José Antonio | es |
dc.date.accessioned | 2023-02-08T14:05:47Z | |
dc.date.available | 2023-02-08T14:05:47Z | |
dc.date.issued | 2013 | |
dc.identifier.citation | Oropesa-Avila, M., Fernandez-Vega, A., De La Mata, M., Maraver, J.G., Cordero, M.D., Cotán, D.,...,Sánchez-Alcázar, J.A. (2013). Apoptotic microtubules delimit an active caspase free area in the cellular cortex during the execution phase of apoptosis. Cell of Death, 4 (1), e527. https://doi.org/10.1038/cddis.2013.58. | |
dc.identifier.issn | 2041-4889 | es |
dc.identifier.uri | https://hdl.handle.net/11441/142549 | |
dc.description.abstract | Apoptotic microtubule network (AMN) is organized during apoptosis, forming a cortical structure beneath plasma membrane,
which has an important role in preserving cell morphology and plasma membrane permeability. The aim of this study was to
examine the role of AMN in maintaining plasma membrane integrity during the execution phase of apoptosis. We demonstrated
in camptothecin-induced apoptosis in H460 cells that AMN delimits an active caspase free area beneath plasma membrane that
permits the preservation of cellular cortex and transmembrane proteins. AMN depolymerization in apoptotic cells by a short
exposure to colchicine allowed active caspases to reach the cellular cortex and cleave many key proteins involved in plasma
membrane structural support, cell adhesion and ionic homeostasis. Cleavage of cellular cortex and plasma membrane proteins,
such as a-spectrin, paxilin, focal adhesion kinase (FAK), E-cadherin and integrin subunit b4 was associated with cell collapse
and cell detachment. Otherwise, cleavage-mediated inactivation of calcium ATPase pump (PMCA-4) and Naþ/Ca2þ exchanger
(NCX) involved in cell calcium extrusion resulted in calcium overload. Furthermore, cleavage of Naþ/Kþ pump subunit b was
associated with altered sodium homeostasis. Cleavage of cell cortex and plasma membrane proteins in apoptotic cells after AMN
depolymerization increased plasma permeability, ionic imbalance and bioenergetic collapse, leading apoptotic cells to
secondary necrosis. The essential role of caspase-mediated cleavage in this process was demonstrated because the
concomitant addition of colchicine that induces AMN depolymerization and the pan-caspase inhibitor z-VAD avoided the
cleavage of cortical and plasma membrane proteins and prevented apoptotic cells to undergo secondary necrosis. Furthermore,
the presence of AMN was also critical for proper phosphatidylserine externalization and apoptotic cell clearance by
macrophages. These results indicate that AMN is essential to preserve an active caspase free area in the cellular cortex of
apoptotic cells that allows plasma membrane integrity during the execution phase of apoptosis. | es |
dc.format | application/pdf | es |
dc.format.extent | 13 p. | es |
dc.language.iso | eng | es |
dc.publisher | NATURE PUBLISHING GROUP | es |
dc.relation.ispartof | Cell of Death, 4 (1), e527. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Experimental medicine | es |
dc.title | Apoptotic microtubules delimit an active caspase free area in the cellular cortex during the execution phase of apoptosis | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica | es |
dc.relation.projectID | FIS PI10/00543 | es |
dc.relation.projectID | FIS EC08/00076 | es |
dc.relation.projectID | SAS 111242 | es |
dc.relation.publisherversion | https://www.nature.com/articles/cddis201358 | es |
dc.identifier.doi | 10.1038/cddis.2013.58 | es |
dc.journaltitle | Cell of Death | es |
dc.publication.volumen | 4 | es |
dc.publication.issue | 1 | es |
dc.publication.initialPage | e527 | es |
dc.contributor.funder | Ministerio de Sanidad. España | es |
dc.contributor.funder | Servicio Andaluz de Salud Junta de Andalucía | es |