| RRC ID |
77496
|
| 著者 |
Toriyama M, Kozawa S, Sakumura Y, Inagaki N.
|
| タイトル |
Conversion of a signal into forces for axon outgrowth through Pak1-mediated shootin1 phosphorylation.
|
| ジャーナル |
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.
|
| 巻・号 |
23(6)
|
| ページ |
529-34
|
| 公開日 |
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
|
| リソース情報 |
| 遺伝子材料 |
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) |
