Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Ke, Lyu, Wanqing, Yu, Ji, Koleske, Anthony J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2018
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
_version_ 1783372838176030720
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
work_keys_str_mv AT zhangke abl2isrecruitedtoventralactinwavesthroughcytoskeletalinteractionstopromotelamellipodiumextension
AT lyuwanqing abl2isrecruitedtoventralactinwavesthroughcytoskeletalinteractionstopromotelamellipodiumextension
AT yuji abl2isrecruitedtoventralactinwavesthroughcytoskeletalinteractionstopromotelamellipodiumextension
AT koleskeanthonyj abl2isrecruitedtoventralactinwavesthroughcytoskeletalinteractionstopromotelamellipodiumextension