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.
The paper is published in the Journal below.
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.