Adhesion-clutch drives three-dimensional axon outgrowth

Abstract

Axon outgrowth requires forces generated by the growth cone. A key model explaining this force generation is the adhesion-clutch mechanism, in which adhesion and clutch molecules convert backward movement of actin filaments into the force that drives axon outgrowth. However, this mechanism has not been validated in three-dimensional (3D) environments. Additionally, a recent study reported that inhibiting actin dynamics or the cell adhesion molecule integrin did not affect axon outgrowth in a 3D collagen gel, challenging the adhesion-clutch paradigm. Here, we show that the adhesion molecule N-cadherin and the clutch molecule shootin1a form a non-integrin adhesion-clutch in a 3D environment containing an appropriate adhesive substrate, N-cadherin. We detected forces produced by growth cones when N-cadherin was present. Furthermore, inhibition of N-cadherin, shootin1a or actin dynamics suppressed 3D axon outgrowth. Our findings demonstrate that the adhesion-clutch is critical machinery for 3D neural network formation under the regulation of specific adhesions.

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BibTeX RIS

BibTeX

@misc{chen2026adhesionclutch,
  title = {{Adhesion-clutch drives three-dimensional axon outgrowth}},
  author = {H. Chen and Z. Qiu and S. Yamada and A. Murakami and T. Minegishi and N. Inagaki},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.07.749764},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.07.749764v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Adhesion-clutch drives three-dimensional axon outgrowth
AU  - H. Chen
AU  - Z. Qiu
AU  - S. Yamada
AU  - A. Murakami
AU  - T. Minegishi
AU  - N. Inagaki
PY  - 2026
DA  - 2026/09/07
PB  - bioRxiv
DO  - 10.64898/2026.09.07.749764
UR  - https://www.biorxiv.org/content/10.64898/2026.09.07.749764v1
AB  - Axon outgrowth requires forces generated by the growth cone. A key model explaining this force generation is the adhesion-clutch mechanism, in which adhesion and clutch molecules convert backward movement of actin filaments into the force that drives axon outgrowth. However, this mechanism has not been validated in three-dimensional (3D) environments. Additionally, a recent study reported that inhibiting actin dynamics or the cell adhesion molecule integrin did not affect axon outgrowth in a 3D collagen gel, challenging the adhesion-clutch paradigm. Here, we show that the adhesion molecule N-cadherin and the clutch molecule shootin1a form a non-integrin adhesion-clutch in a 3D environment containing an appropriate adhesive substrate, N-cadherin. We detected forces produced by growth cones when N-cadherin was present. Furthermore, inhibition of N-cadherin, shootin1a or actin dynamics suppressed 3D axon outgrowth. Our findings demonstrate that the adhesion-clutch is critical machinery for 3D neural network formation under the regulation of specific adhesions.
ER  -

Abstract

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