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Abl2 is recruited to ventral actin waves through cytoskeletal interactions to promote lamellipodium extension
Abl family nonreceptor tyrosine kinases regulate changes in cell shape and migration. Abl2 localizes to dynamic actin-rich protrusions, such as lamellipodia in fibroblasts and dendritic spines in neurons. Abl2 interactions with cortactin, an actin filament stabilizer, are crucial for the formation a...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249870/ https://www.ncbi.nlm.nih.gov/pubmed/30256707 http://dx.doi.org/10.1091/mbc.E18-01-0044 |
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author | Zhang, Ke Lyu, Wanqing Yu, Ji Koleske, Anthony J. |
author_facet | Zhang, Ke Lyu, Wanqing Yu, Ji Koleske, Anthony J. |
author_sort | Zhang, Ke |
collection | PubMed |
description | Abl family nonreceptor tyrosine kinases regulate changes in cell shape and migration. Abl2 localizes to dynamic actin-rich protrusions, such as lamellipodia in fibroblasts and dendritic spines in neurons. Abl2 interactions with cortactin, an actin filament stabilizer, are crucial for the formation and stability of actin-rich structures, but Abl2:cortactin-positive structures have not been characterized with high spatiotemporal resolution in cells. Using total internal reflection fluorescence microscopy, we demonstrate that Abl2 colocalizes with cortactin at wave-like structures within lamellum and lamellipodium tips. Abl2 and cortactin within waves are focal and transient, extend to the outer edge of lamella, and serve as the base for lamellipodia protrusions. Abl2-positive foci colocalize with integrin β3 and paxillin, adhesive markers of the lamellum–lamellipodium interface. Cortactin-positive waves still form in Abl2 knockout cells, but the lamellipodium size is significantly reduced. This deficiency is restored following Abl2 reexpression. Complementation analyses revealed that the Abl2 C-terminal half, which contains domains that bind actin and microtubules, is necessary and sufficient for recruitment to the wave-like structures and to support normal lamellipodium size, while the kinase domain–containing N-terminal half does not impact lamellipodium size. Together, this work demonstrates that Abl2 is recruited with cortactin to actin waves through cytoskeletal interactions to promote lamellipodium extension. |
format | Online Article Text |
id | pubmed-6249870 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-62498702019-01-30 Abl2 is recruited to ventral actin waves through cytoskeletal interactions to promote lamellipodium extension Zhang, Ke Lyu, Wanqing Yu, Ji Koleske, Anthony J. Mol Biol Cell Articles Abl family nonreceptor tyrosine kinases regulate changes in cell shape and migration. Abl2 localizes to dynamic actin-rich protrusions, such as lamellipodia in fibroblasts and dendritic spines in neurons. Abl2 interactions with cortactin, an actin filament stabilizer, are crucial for the formation and stability of actin-rich structures, but Abl2:cortactin-positive structures have not been characterized with high spatiotemporal resolution in cells. Using total internal reflection fluorescence microscopy, we demonstrate that Abl2 colocalizes with cortactin at wave-like structures within lamellum and lamellipodium tips. Abl2 and cortactin within waves are focal and transient, extend to the outer edge of lamella, and serve as the base for lamellipodia protrusions. Abl2-positive foci colocalize with integrin β3 and paxillin, adhesive markers of the lamellum–lamellipodium interface. Cortactin-positive waves still form in Abl2 knockout cells, but the lamellipodium size is significantly reduced. This deficiency is restored following Abl2 reexpression. Complementation analyses revealed that the Abl2 C-terminal half, which contains domains that bind actin and microtubules, is necessary and sufficient for recruitment to the wave-like structures and to support normal lamellipodium size, while the kinase domain–containing N-terminal half does not impact lamellipodium size. Together, this work demonstrates that Abl2 is recruited with cortactin to actin waves through cytoskeletal interactions to promote lamellipodium extension. The American Society for Cell Biology 2018-11-15 /pmc/articles/PMC6249870/ /pubmed/30256707 http://dx.doi.org/10.1091/mbc.E18-01-0044 Text en © 2018 Zhang et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Articles Zhang, Ke Lyu, Wanqing Yu, Ji Koleske, Anthony J. Abl2 is recruited to ventral actin waves through cytoskeletal interactions to promote lamellipodium extension |
title | Abl2 is recruited to ventral actin waves through cytoskeletal interactions to promote lamellipodium extension |
title_full | Abl2 is recruited to ventral actin waves through cytoskeletal interactions to promote lamellipodium extension |
title_fullStr | Abl2 is recruited to ventral actin waves through cytoskeletal interactions to promote lamellipodium extension |
title_full_unstemmed | Abl2 is recruited to ventral actin waves through cytoskeletal interactions to promote lamellipodium extension |
title_short | Abl2 is recruited to ventral actin waves through cytoskeletal interactions to promote lamellipodium extension |
title_sort | abl2 is recruited to ventral actin waves through cytoskeletal interactions to promote lamellipodium extension |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249870/ https://www.ncbi.nlm.nih.gov/pubmed/30256707 http://dx.doi.org/10.1091/mbc.E18-01-0044 |
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