| RRC ID |
77498
|
| 著者 |
Baba K, Yoshida W, Toriyama M, Shimada T, Manning CF, Saito M, Kohno K, Trimmer JS, Watanabe R, Inagaki N.
|
| タイトル |
Gradient-reading and mechano-effector machinery for netrin-1-induced axon guidance.
|
| ジャーナル |
Elife
|
| Abstract |
Growth cones navigate axonal projection in response to guidance cues. However, it is unclear how they can decide the migratory direction by transducing the local spatial cues into protrusive forces. Here we show that knockout mice of Shootin1 display abnormal projection of the forebrain commissural axons, a phenotype similar to that of the axon guidance molecule netrin-1. Shallow gradients of netrin-1 elicited highly polarized Pak1-mediated phosphorylation of shootin1 within growth cones. We demonstrate that netrin-1-elicited shootin1 phosphorylation increases shootin1 interaction with the cell adhesion molecule L1-CAM; this, in turn, promotes F-actin-adhesion coupling and concomitant generation of forces for growth cone migration. Moreover, the spatially regulated shootin1 phosphorylation within growth cones is required for axon turning induced by netrin-1 gradients. Our study defines a mechano-effector for netrin-1 signaling and demonstrates that shootin1 phosphorylation is a critical readout for netrin-1 gradients that results in a directional mechanoresponse for axon guidance.
|
| 巻・号 |
7
|
| 公開日 |
2018-8-7
|
| DOI |
10.7554/eLife.34593
|
| PII |
34593
|
| PMID |
30082022
|
| PMC |
PMC6080949
|
| MeSH |
Actins / metabolism
Animals
Axon Guidance / physiology*
Cell Adhesion
Cells, Cultured
Chemotaxis*
Embryo, Mammalian / cytology
Embryo, Mammalian / physiology*
Growth Cones / physiology*
Mechanotransduction, Cellular*
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Tissue Proteins / physiology*
Netrin-1 / genetics
Netrin-1 / metabolism*
Neural Cell Adhesion Molecule L1 / metabolism
Phosphorylation
Rats
Rats, Wistar
Signal Transduction
p21-Activated Kinases / genetics
p21-Activated Kinases / metabolism
|
| IF |
7.08
|
| リソース情報 |
| 遺伝子材料 |
pCAGGS-myc-shootin1a (1-125) (RDB19944) |
