Conversion of a signal into forces for axon outgrowth through Pak1-mediated shootin1 phosphorylation

Curr Biol. 2013 Mar 18;23(6):529-34. doi: 10.1016/j.cub.2013.02.017. Epub 2013 Feb 28.


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 [1, 2]; this, together with myosin II activity, induces retrograde flow of F-actins [3-5]. 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 [6-10]. However, how cell signaling controls the coupling efficiency remains unknown. Shootin1 functions as a linker molecule that couples F-actin retrograde flow and the substrate at neuronal growth cones to promote axon outgrowth [11]. Here we show that shootin1 is located at a critical interface, transducing a chemical signal into traction forces for axon outgrowth. We found that a chemoattractant, 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 results 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Cells, Cultured
  • Growth Cones / physiology*
  • Hippocampus / growth & development
  • Hippocampus / physiology
  • Mass Spectrometry
  • Nerve Growth Factors / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Netrin-1
  • Phosphorylation
  • Rats
  • Signal Transduction*
  • Tumor Suppressor Proteins / metabolism*
  • p21-Activated Kinases / metabolism*


  • Actins
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Ntn1 protein, rat
  • Shtn1 protein, rat
  • Tumor Suppressor Proteins
  • Netrin-1
  • Pak1 protein, rat
  • p21-Activated Kinases