論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Wikipedia |
| 各媒体での言及数の合計 | 12 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| 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) (RDB20284) |