Adhesion-clutch drives three-dimensional axon outgrowth
Description
Axon outgrowth requires forces generated by the growth cone. A key model explaining this force generation is the adhesion-clutch mechanism, through which the backward force of treadmilling actin filaments is transmitted to the extracellular environment via adhesion and clutch molecules. 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 inhibited 3D axon outgrowth. Our findings demonstrate that the adhesion-clutch is a critical machinery for 3D neural network formation under the regulation of specific adhesions.