RGD Reference Report - Conversion of a signal into forces for axon outgrowth through Pak1-mediated shootin1 phosphorylation. - Rat Genome Database

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

Authors: Toriyama, M  Kozawa, S  Sakumura, Y  Inagaki, N 
Citation: Toriyama M, etal., Curr Biol. 2013 Mar 18;23(6):529-34. doi: 10.1016/j.cub.2013.02.017. Epub 2013 Feb 28.
RGD ID: 10054078
Pubmed: (View Article at PubMed) PMID:23453953
DOI: Full-text: DOI:10.1016/j.cub.2013.02.017

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.

Annotation

Gene Ontology Annotations    

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Ntn1  (netrin 1)
Pak1  (p21 (RAC1) activated kinase 1)
Shtn1  (shootin 1)


Additional Information