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The role of nonmuscle myosin 2A and 2B in the regulation of mesenchymal cell contact guidance

Contact guidance refers to the ability of cells to sense the geometrical features of the microenvironment and respond by changing their shape and adopting the appropriate orientation. Inhibition and ablation of nonmuscle myosin 2 (NM2) paralogues have demonstrated their importance for contact guidan...

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Autores principales: Zhovmer, Alexander S., Tabdanov, Erdem D., Miao, Houxun, Wen, Han, Chen, Jinqiu, Luo, Xiaoling, Ma, Xuefei, Provenzano, Paolo P., Adelstein, Robert S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727766/
https://www.ncbi.nlm.nih.gov/pubmed/31318315
http://dx.doi.org/10.1091/mbc.E19-01-0071
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author Zhovmer, Alexander S.
Tabdanov, Erdem D.
Miao, Houxun
Wen, Han
Chen, Jinqiu
Luo, Xiaoling
Ma, Xuefei
Provenzano, Paolo P.
Adelstein, Robert S.
author_facet Zhovmer, Alexander S.
Tabdanov, Erdem D.
Miao, Houxun
Wen, Han
Chen, Jinqiu
Luo, Xiaoling
Ma, Xuefei
Provenzano, Paolo P.
Adelstein, Robert S.
author_sort Zhovmer, Alexander S.
collection PubMed
description Contact guidance refers to the ability of cells to sense the geometrical features of the microenvironment and respond by changing their shape and adopting the appropriate orientation. Inhibition and ablation of nonmuscle myosin 2 (NM2) paralogues have demonstrated their importance for contact guidance. However, the specific roles of the NM2 paralogues have not been systematically studied. In this work we use micropatterned substrates to examine the roles of NM2A and NM2B and to elucidate the relationship of the microenvironment, actomyosin, and microtubules in contact guidance. We show that contact guidance is preserved following loss of NM2B and that expression of NM2A alone is sufficient to establish an appropriate orientation of the cells. Loss of NM2B and overexpression of NM2A result in a prominent cell polarization that is found to be linked to the increased alignment of microtubules with the actomyosin scaffold. Suppression of actomyosin with blebbistatin reduces cell polarity on a flat surface, but not on a surface with contact guidance cues. This indicates that the lost microtubule–actomyosin interactions are compensated for by microtubule–microenvironment interactions, which are sufficient to establish cell polarity through contact guidance.
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spelling pubmed-67277662019-10-07 The role of nonmuscle myosin 2A and 2B in the regulation of mesenchymal cell contact guidance Zhovmer, Alexander S. Tabdanov, Erdem D. Miao, Houxun Wen, Han Chen, Jinqiu Luo, Xiaoling Ma, Xuefei Provenzano, Paolo P. Adelstein, Robert S. Mol Biol Cell Articles Contact guidance refers to the ability of cells to sense the geometrical features of the microenvironment and respond by changing their shape and adopting the appropriate orientation. Inhibition and ablation of nonmuscle myosin 2 (NM2) paralogues have demonstrated their importance for contact guidance. However, the specific roles of the NM2 paralogues have not been systematically studied. In this work we use micropatterned substrates to examine the roles of NM2A and NM2B and to elucidate the relationship of the microenvironment, actomyosin, and microtubules in contact guidance. We show that contact guidance is preserved following loss of NM2B and that expression of NM2A alone is sufficient to establish an appropriate orientation of the cells. Loss of NM2B and overexpression of NM2A result in a prominent cell polarization that is found to be linked to the increased alignment of microtubules with the actomyosin scaffold. Suppression of actomyosin with blebbistatin reduces cell polarity on a flat surface, but not on a surface with contact guidance cues. This indicates that the lost microtubule–actomyosin interactions are compensated for by microtubule–microenvironment interactions, which are sufficient to establish cell polarity through contact guidance. The American Society for Cell Biology 2019-07-22 /pmc/articles/PMC6727766/ /pubmed/31318315 http://dx.doi.org/10.1091/mbc.E19-01-0071 Text en © 2019 Zhovmer 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
Zhovmer, Alexander S.
Tabdanov, Erdem D.
Miao, Houxun
Wen, Han
Chen, Jinqiu
Luo, Xiaoling
Ma, Xuefei
Provenzano, Paolo P.
Adelstein, Robert S.
The role of nonmuscle myosin 2A and 2B in the regulation of mesenchymal cell contact guidance
title The role of nonmuscle myosin 2A and 2B in the regulation of mesenchymal cell contact guidance
title_full The role of nonmuscle myosin 2A and 2B in the regulation of mesenchymal cell contact guidance
title_fullStr The role of nonmuscle myosin 2A and 2B in the regulation of mesenchymal cell contact guidance
title_full_unstemmed The role of nonmuscle myosin 2A and 2B in the regulation of mesenchymal cell contact guidance
title_short The role of nonmuscle myosin 2A and 2B in the regulation of mesenchymal cell contact guidance
title_sort role of nonmuscle myosin 2a and 2b in the regulation of mesenchymal cell contact guidance
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727766/
https://www.ncbi.nlm.nih.gov/pubmed/31318315
http://dx.doi.org/10.1091/mbc.E19-01-0071
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