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Mechanosensitive axon outgrowth mediated by L1-laminin clutch interface

Mechanical properties of the extracellular environment modulate axon outgrowth. Growth cones at the tip of extending axons generate traction force for axon outgrowth by transmitting the force of actin filament retrograde flow, produced by actomyosin contraction and F-actin polymerization, to adhesiv...

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Autores principales: Abe, Kouki, Baba, Kentarou, Huang, Liguo, Wei, Koay Teng, Okano, Kazunori, Hosokawa, Yoichiroh, Inagaki, Naoyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Biophysical Society 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456307/
https://www.ncbi.nlm.nih.gov/pubmed/34384760
http://dx.doi.org/10.1016/j.bpj.2021.08.009
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author Abe, Kouki
Baba, Kentarou
Huang, Liguo
Wei, Koay Teng
Okano, Kazunori
Hosokawa, Yoichiroh
Inagaki, Naoyuki
author_facet Abe, Kouki
Baba, Kentarou
Huang, Liguo
Wei, Koay Teng
Okano, Kazunori
Hosokawa, Yoichiroh
Inagaki, Naoyuki
author_sort Abe, Kouki
collection PubMed
description Mechanical properties of the extracellular environment modulate axon outgrowth. Growth cones at the tip of extending axons generate traction force for axon outgrowth by transmitting the force of actin filament retrograde flow, produced by actomyosin contraction and F-actin polymerization, to adhesive substrates through clutch and cell adhesion molecules. A molecular clutch between the actin filament flow and substrate is proposed to contribute to cellular mechanosensing. However, the molecular identity of the clutch interface responsible for mechanosensitive growth cone advance is unknown. We previously reported that mechanical coupling between actin filament retrograde flow and adhesive substrates through the clutch molecule shootin1a and the cell adhesion molecule L1 generates traction force for axon outgrowth and guidance. Here, we show that cultured mouse hippocampal neurons extend longer axons on stiffer substrates under elastic conditions that correspond to the soft brain environments. We demonstrate that this stiffness-dependent axon outgrowth requires actin-adhesion coupling mediated by shootin1a, L1, and laminin on the substrate. Speckle imaging analyses showed that L1 at the growth cone membrane switches between two adhesive states: L1 that is immobilized and that undergoes retrograde movement on the substrate. The duration of the immobilized phase was longer on stiffer substrates; this was accompanied by increases in actin-adhesion coupling and in the traction force exerted on the substrate. These data suggest that the interaction between L1 and laminin is enhanced on stiffer substrates, thereby promoting force generation for axon outgrowth.
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spelling pubmed-84563072022-09-07 Mechanosensitive axon outgrowth mediated by L1-laminin clutch interface Abe, Kouki Baba, Kentarou Huang, Liguo Wei, Koay Teng Okano, Kazunori Hosokawa, Yoichiroh Inagaki, Naoyuki Biophys J Article Mechanical properties of the extracellular environment modulate axon outgrowth. Growth cones at the tip of extending axons generate traction force for axon outgrowth by transmitting the force of actin filament retrograde flow, produced by actomyosin contraction and F-actin polymerization, to adhesive substrates through clutch and cell adhesion molecules. A molecular clutch between the actin filament flow and substrate is proposed to contribute to cellular mechanosensing. However, the molecular identity of the clutch interface responsible for mechanosensitive growth cone advance is unknown. We previously reported that mechanical coupling between actin filament retrograde flow and adhesive substrates through the clutch molecule shootin1a and the cell adhesion molecule L1 generates traction force for axon outgrowth and guidance. Here, we show that cultured mouse hippocampal neurons extend longer axons on stiffer substrates under elastic conditions that correspond to the soft brain environments. We demonstrate that this stiffness-dependent axon outgrowth requires actin-adhesion coupling mediated by shootin1a, L1, and laminin on the substrate. Speckle imaging analyses showed that L1 at the growth cone membrane switches between two adhesive states: L1 that is immobilized and that undergoes retrograde movement on the substrate. The duration of the immobilized phase was longer on stiffer substrates; this was accompanied by increases in actin-adhesion coupling and in the traction force exerted on the substrate. These data suggest that the interaction between L1 and laminin is enhanced on stiffer substrates, thereby promoting force generation for axon outgrowth. The Biophysical Society 2021-09-07 2021-08-10 /pmc/articles/PMC8456307/ /pubmed/34384760 http://dx.doi.org/10.1016/j.bpj.2021.08.009 Text en © 2021 Biophysical Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Abe, Kouki
Baba, Kentarou
Huang, Liguo
Wei, Koay Teng
Okano, Kazunori
Hosokawa, Yoichiroh
Inagaki, Naoyuki
Mechanosensitive axon outgrowth mediated by L1-laminin clutch interface
title Mechanosensitive axon outgrowth mediated by L1-laminin clutch interface
title_full Mechanosensitive axon outgrowth mediated by L1-laminin clutch interface
title_fullStr Mechanosensitive axon outgrowth mediated by L1-laminin clutch interface
title_full_unstemmed Mechanosensitive axon outgrowth mediated by L1-laminin clutch interface
title_short Mechanosensitive axon outgrowth mediated by L1-laminin clutch interface
title_sort mechanosensitive axon outgrowth mediated by l1-laminin clutch interface
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456307/
https://www.ncbi.nlm.nih.gov/pubmed/34384760
http://dx.doi.org/10.1016/j.bpj.2021.08.009
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