Mechanism for signal-force transduction in axon outgrowth (March 01, 2013)

Soluble guidance cues can direct cellular protrusion and migration by modulating adhesion and cytoskeletal dynamics. Actin filaments (F-actins) polymerize at the leading edge of motile cells and depolymerize proximally; this, together with myosin II activity, induces retrograde flow of F-actins. It has been proposed that the traction forces underlying cellular motility may be regulated by the modulation of coupling efficiency between F-actin flow and the extracellular substrate via “clutch” molecules. However, how cell signaling controls the coupling efficiency remains unknown.

Associate professor Naoyuki Inagaki, post-doc researcher Michinori Toriyama in the Laboratory of Neuronal Cell Morphogenesis, Graduate School of Biological Sciences, and coworkers have found that shootin1 is located at a critical interface, transducing a chemical signal into traction forces for axon outgrowth. Shootin1 functions as a “clutch” molecule that couples F-actin retrograde flow and the substrate at neuronal growth cones to promote axon outgrowth. The group found that an attractive axon guidance cue, netrin-1, positively regulates traction forces at axonal growth cones via Pak1-mediated shootin1 phosphorylation. This phosphorylation enhanced the interaction between shootin1 and F-actin retrograde flow, thereby promoting F-actin-substrate coupling, force generation, and concomitant filopodium extension and axon outgrowth. These findings suggest that dynamic actin-substrate coupling can transduce chemical signals into mechanical forces to control cellular motility, and provide a molecular-level description of how this transduction may occur.

【Related link】
The paper is published in the Journal below.
http://www.cell.com/current-biology/abstract/S0960-9822(13)00188-7

Here is the bibliographic information of the paper.
Michinori Toriyama, Satoshi Kozawa, Yuichi Sakumura, and Naoyuki Inagaki, Conversion of a Signal into Forces for Axon Outgrowth through Pak1-Mediated Shootin1 Phosphorylation. Current Biology 23, 529-534, 2013.

An axonal growth cone (axonal tip) of a cultured rat hippocampal neuron. Shootin1 phosphorylated by PAK1 (green) interacts with F-actins (red) to transduce Netrin1 signaling into force for axon outgrowth. Blue: microtubules.
An axonal growth cone (axonal tip) of a cultured rat hippocampal neuron. Shootin1 phosphorylated by PAK1 (green) interacts with F-actins (red) to transduce Netrin1 signaling into force for axon outgrowth. Blue: microtubules.
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