RRC ID 77496
Author Toriyama M, Kozawa S, Sakumura Y, Inagaki N.
Title Conversion of a signal into forces for axon outgrowth through Pak1-mediated shootin1 phosphorylation.
Journal Curr Biol
Abstract 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.
Volume 23(6)
Pages 529-34
Published 2013-3-18
DOI 10.1016/j.cub.2013.02.017
PII S0960-9822(13)00188-7
PMID 23453953
MeSH 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*
IF 9.601
DNA material pCMV-myc-shootin1a (S101D, S249D) (RDB19947) pCMV-myc-shootin1a (S101A, S249A) (RDB19948) pCMV-myc-RNAi refractory shootin1a (S101D, S249D) (RDB19951) pCMV-myc-RNAi refractory shootin1a (S101A, S249A) (RDB19952)