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In vivo epidermal migration requires focal adhesion targeting of ACF7

Turnover of focal adhesions allows cell retraction, which is essential for cell migration. The mammalian spectraplakin protein, ACF7 (Actin-Crosslinking Factor 7), promotes focal adhesion dynamics by targeting of microtubule plus ends towards focal adhesions. However, it remains unclear how the acti...

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Autores principales: Yue, Jiping, Zhang, Yao, Liang, Wenguang G., Gou, Xuewen, Lee, Philbert, Liu, Han, Lyu, Wanqing, Tang, Wei-Jen, Chen, Shao-Yu, Yang, Feng, Liang, Hong, Wu, Xiaoyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476826/
https://www.ncbi.nlm.nih.gov/pubmed/27216888
http://dx.doi.org/10.1038/ncomms11692
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author Yue, Jiping
Zhang, Yao
Liang, Wenguang G.
Gou, Xuewen
Lee, Philbert
Liu, Han
Lyu, Wanqing
Tang, Wei-Jen
Chen, Shao-Yu
Yang, Feng
Liang, Hong
Wu, Xiaoyang
author_facet Yue, Jiping
Zhang, Yao
Liang, Wenguang G.
Gou, Xuewen
Lee, Philbert
Liu, Han
Lyu, Wanqing
Tang, Wei-Jen
Chen, Shao-Yu
Yang, Feng
Liang, Hong
Wu, Xiaoyang
author_sort Yue, Jiping
collection PubMed
description Turnover of focal adhesions allows cell retraction, which is essential for cell migration. The mammalian spectraplakin protein, ACF7 (Actin-Crosslinking Factor 7), promotes focal adhesion dynamics by targeting of microtubule plus ends towards focal adhesions. However, it remains unclear how the activity of ACF7 is regulated spatiotemporally to achieve focal adhesion-specific guidance of microtubule. To explore the potential mechanisms, we resolve the crystal structure of ACF7’s NT (amino-terminal) domain, which mediates F-actin interactions. Structural analysis leads to identification of a key tyrosine residue at the calponin homology (CH) domain of ACF7, whose phosphorylation by Src/FAK (focal adhesion kinase) complex is essential for F-actin binding of ACF7. Using skin epidermis as a model system, we further demonstrate that the phosphorylation of ACF7 plays an indispensable role in focal adhesion dynamics and epidermal migration in vitro and in vivo. Together, our findings provide critical insights into the molecular mechanisms underlying coordinated cytoskeletal dynamics during cell movement.
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spelling pubmed-54768262017-07-03 In vivo epidermal migration requires focal adhesion targeting of ACF7 Yue, Jiping Zhang, Yao Liang, Wenguang G. Gou, Xuewen Lee, Philbert Liu, Han Lyu, Wanqing Tang, Wei-Jen Chen, Shao-Yu Yang, Feng Liang, Hong Wu, Xiaoyang Nat Commun Article Turnover of focal adhesions allows cell retraction, which is essential for cell migration. The mammalian spectraplakin protein, ACF7 (Actin-Crosslinking Factor 7), promotes focal adhesion dynamics by targeting of microtubule plus ends towards focal adhesions. However, it remains unclear how the activity of ACF7 is regulated spatiotemporally to achieve focal adhesion-specific guidance of microtubule. To explore the potential mechanisms, we resolve the crystal structure of ACF7’s NT (amino-terminal) domain, which mediates F-actin interactions. Structural analysis leads to identification of a key tyrosine residue at the calponin homology (CH) domain of ACF7, whose phosphorylation by Src/FAK (focal adhesion kinase) complex is essential for F-actin binding of ACF7. Using skin epidermis as a model system, we further demonstrate that the phosphorylation of ACF7 plays an indispensable role in focal adhesion dynamics and epidermal migration in vitro and in vivo. Together, our findings provide critical insights into the molecular mechanisms underlying coordinated cytoskeletal dynamics during cell movement. Nature Publishing Group 2016-05-24 /pmc/articles/PMC5476826/ /pubmed/27216888 http://dx.doi.org/10.1038/ncomms11692 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Yue, Jiping
Zhang, Yao
Liang, Wenguang G.
Gou, Xuewen
Lee, Philbert
Liu, Han
Lyu, Wanqing
Tang, Wei-Jen
Chen, Shao-Yu
Yang, Feng
Liang, Hong
Wu, Xiaoyang
In vivo epidermal migration requires focal adhesion targeting of ACF7
title In vivo epidermal migration requires focal adhesion targeting of ACF7
title_full In vivo epidermal migration requires focal adhesion targeting of ACF7
title_fullStr In vivo epidermal migration requires focal adhesion targeting of ACF7
title_full_unstemmed In vivo epidermal migration requires focal adhesion targeting of ACF7
title_short In vivo epidermal migration requires focal adhesion targeting of ACF7
title_sort in vivo epidermal migration requires focal adhesion targeting of acf7
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476826/
https://www.ncbi.nlm.nih.gov/pubmed/27216888
http://dx.doi.org/10.1038/ncomms11692
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