Gradient-reading and mechano-effector machinery for netrin-1-induced axon guidance

Kentarou Baba, Wataru Yoshida, Michinori Toriyama, Tadayuki Shimada, Colleen F. Manning, Michiko Saito, Kenji Kohno, James Trimmer, Rikiya Watanabe, Naoyuki Inagaki

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere34593
JournaleLife
Volume7
DOIs
StatePublished - Aug 7 2018

Fingerprint

Machinery
Reading
Growth Cones
Phosphorylation
Cones
Cues
Axons
Neural Cell Adhesion Molecule L1
Computer aided manufacturing
Prosencephalon
Knockout Mice
Axon Guidance
netrin-1
Actins
Adhesion
Phenotype
Molecules

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Baba, K., Yoshida, W., Toriyama, M., Shimada, T., Manning, C. F., Saito, M., ... Inagaki, N. (2018). Gradient-reading and mechano-effector machinery for netrin-1-induced axon guidance. eLife, 7, [e34593]. https://doi.org/10.7554/eLife.34593

Gradient-reading and mechano-effector machinery for netrin-1-induced axon guidance. / Baba, Kentarou; Yoshida, Wataru; Toriyama, Michinori; Shimada, Tadayuki; Manning, Colleen F.; Saito, Michiko; Kohno, Kenji; Trimmer, James; Watanabe, Rikiya; Inagaki, Naoyuki.

In: eLife, Vol. 7, e34593, 07.08.2018.

Research output: Contribution to journalArticle

Baba, K, Yoshida, W, Toriyama, M, Shimada, T, Manning, CF, Saito, M, Kohno, K, Trimmer, J, Watanabe, R & Inagaki, N 2018, 'Gradient-reading and mechano-effector machinery for netrin-1-induced axon guidance', eLife, vol. 7, e34593. https://doi.org/10.7554/eLife.34593
Baba K, Yoshida W, Toriyama M, Shimada T, Manning CF, Saito M et al. Gradient-reading and mechano-effector machinery for netrin-1-induced axon guidance. eLife. 2018 Aug 7;7. e34593. https://doi.org/10.7554/eLife.34593
Baba, Kentarou ; Yoshida, Wataru ; Toriyama, Michinori ; Shimada, Tadayuki ; Manning, Colleen F. ; Saito, Michiko ; Kohno, Kenji ; Trimmer, James ; Watanabe, Rikiya ; Inagaki, Naoyuki. / Gradient-reading and mechano-effector machinery for netrin-1-induced axon guidance. In: eLife. 2018 ; Vol. 7.
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