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Forces drive basement membrane invasion in Caenorhabditis elegans

During invasion, cells breach basement membrane (BM) barriers with actin-rich protrusions. It remains unclear, however, whether actin polymerization applies pushing forces to help break through BM, or whether actin filaments play a passive role as scaffolding for targeting invasive machinery. Here,...

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Autores principales: Cáceres, Rodrigo, Bojanala, Nagagireesh, Kelley, Laura C., Dreier, Jes, Manzi, John, Di Federico, Fahima, Chi, Qiuyi, Risler, Thomas, Testa, Ilaria, Sherwood, David R., Plastino, Julie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233148/
https://www.ncbi.nlm.nih.gov/pubmed/30348801
http://dx.doi.org/10.1073/pnas.1808760115
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author Cáceres, Rodrigo
Bojanala, Nagagireesh
Kelley, Laura C.
Dreier, Jes
Manzi, John
Di Federico, Fahima
Chi, Qiuyi
Risler, Thomas
Testa, Ilaria
Sherwood, David R.
Plastino, Julie
author_facet Cáceres, Rodrigo
Bojanala, Nagagireesh
Kelley, Laura C.
Dreier, Jes
Manzi, John
Di Federico, Fahima
Chi, Qiuyi
Risler, Thomas
Testa, Ilaria
Sherwood, David R.
Plastino, Julie
author_sort Cáceres, Rodrigo
collection PubMed
description During invasion, cells breach basement membrane (BM) barriers with actin-rich protrusions. It remains unclear, however, whether actin polymerization applies pushing forces to help break through BM, or whether actin filaments play a passive role as scaffolding for targeting invasive machinery. Here, using the developmental event of anchor cell (AC) invasion in Caenorhabditis elegans, we observe that the AC deforms the BM and underlying tissue just before invasion, exerting forces in the tens of nanonewtons range. Deformation is driven by actin polymerization nucleated by the Arp2/3 complex and its activators, whereas formins and cross-linkers are dispensable. Delays in invasion upon actin regulator loss are not caused by defects in AC polarity, trafficking, or secretion, as appropriate markers are correctly localized in the AC even when actin is reduced and invasion is disrupted. Overall force production emerges from this study as one of the main tools that invading cells use to promote BM disruption in C. elegans.
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spelling pubmed-62331482018-11-14 Forces drive basement membrane invasion in Caenorhabditis elegans Cáceres, Rodrigo Bojanala, Nagagireesh Kelley, Laura C. Dreier, Jes Manzi, John Di Federico, Fahima Chi, Qiuyi Risler, Thomas Testa, Ilaria Sherwood, David R. Plastino, Julie Proc Natl Acad Sci U S A Biological Sciences During invasion, cells breach basement membrane (BM) barriers with actin-rich protrusions. It remains unclear, however, whether actin polymerization applies pushing forces to help break through BM, or whether actin filaments play a passive role as scaffolding for targeting invasive machinery. Here, using the developmental event of anchor cell (AC) invasion in Caenorhabditis elegans, we observe that the AC deforms the BM and underlying tissue just before invasion, exerting forces in the tens of nanonewtons range. Deformation is driven by actin polymerization nucleated by the Arp2/3 complex and its activators, whereas formins and cross-linkers are dispensable. Delays in invasion upon actin regulator loss are not caused by defects in AC polarity, trafficking, or secretion, as appropriate markers are correctly localized in the AC even when actin is reduced and invasion is disrupted. Overall force production emerges from this study as one of the main tools that invading cells use to promote BM disruption in C. elegans. National Academy of Sciences 2018-11-06 2018-10-22 /pmc/articles/PMC6233148/ /pubmed/30348801 http://dx.doi.org/10.1073/pnas.1808760115 Text en Copyright © 2018 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Cáceres, Rodrigo
Bojanala, Nagagireesh
Kelley, Laura C.
Dreier, Jes
Manzi, John
Di Federico, Fahima
Chi, Qiuyi
Risler, Thomas
Testa, Ilaria
Sherwood, David R.
Plastino, Julie
Forces drive basement membrane invasion in Caenorhabditis elegans
title Forces drive basement membrane invasion in Caenorhabditis elegans
title_full Forces drive basement membrane invasion in Caenorhabditis elegans
title_fullStr Forces drive basement membrane invasion in Caenorhabditis elegans
title_full_unstemmed Forces drive basement membrane invasion in Caenorhabditis elegans
title_short Forces drive basement membrane invasion in Caenorhabditis elegans
title_sort forces drive basement membrane invasion in caenorhabditis elegans
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233148/
https://www.ncbi.nlm.nih.gov/pubmed/30348801
http://dx.doi.org/10.1073/pnas.1808760115
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