Gradient-reading and mechano-effector machinery for netrin-1-induced axon guidance
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...
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doaj-95e8fa5b09fe4b018a66ee0b2b4b7e302021-05-05T16:04:29ZengeLife Sciences Publications LtdeLife2050-084X2018-08-01710.7554/eLife.34593Gradient-reading and mechano-effector machinery for netrin-1-induced axon guidanceKentarou Baba0Wataru Yoshida1Michinori Toriyama2Tadayuki Shimada3https://orcid.org/0000-0001-7333-9847Colleen F Manning4Michiko Saito5https://orcid.org/0000-0002-6678-2135Kenji Kohno6https://orcid.org/0000-0002-3503-6551James S Trimmer7https://orcid.org/0000-0002-6117-3912Rikiya Watanabe8Naoyuki Inagaki9https://orcid.org/0000-0002-2664-9196Division of Biological Science, Nara Institute of Science and Technology, Ikoma, JapanDivision of Biological Science, Nara Institute of Science and Technology, Ikoma, JapanDivision of Biological Science, Nara Institute of Science and Technology, Ikoma, JapanDivision of Biological Science, Nara Institute of Science and Technology, Ikoma, JapanDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United StatesDivision of Biological Science, Nara Institute of Science and Technology, Ikoma, JapanDivision of Biological Science, Nara Institute of Science and Technology, Ikoma, JapanDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United StatesDepartment of Applied Chemistry, Graduate School of Engineering, University of Tokyo, Tokyo, JapanDivision of Biological Science, Nara Institute of Science and Technology, Ikoma, JapanGrowth 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.https://elifesciences.org/articles/34593axon guidancechemotaxisgrowth conegradient sensingshootin1clutch |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kentarou Baba Wataru Yoshida Michinori Toriyama Tadayuki Shimada Colleen F Manning Michiko Saito Kenji Kohno James S Trimmer Rikiya Watanabe Naoyuki Inagaki |
spellingShingle |
Kentarou Baba Wataru Yoshida Michinori Toriyama Tadayuki Shimada Colleen F Manning Michiko Saito Kenji Kohno James S Trimmer Rikiya Watanabe Naoyuki Inagaki Gradient-reading and mechano-effector machinery for netrin-1-induced axon guidance eLife axon guidance chemotaxis growth cone gradient sensing shootin1 clutch |
author_facet |
Kentarou Baba Wataru Yoshida Michinori Toriyama Tadayuki Shimada Colleen F Manning Michiko Saito Kenji Kohno James S Trimmer Rikiya Watanabe Naoyuki Inagaki |
author_sort |
Kentarou Baba |
title |
Gradient-reading and mechano-effector machinery for netrin-1-induced axon guidance |
title_short |
Gradient-reading and mechano-effector machinery for netrin-1-induced axon guidance |
title_full |
Gradient-reading and mechano-effector machinery for netrin-1-induced axon guidance |
title_fullStr |
Gradient-reading and mechano-effector machinery for netrin-1-induced axon guidance |
title_full_unstemmed |
Gradient-reading and mechano-effector machinery for netrin-1-induced axon guidance |
title_sort |
gradient-reading and mechano-effector machinery for netrin-1-induced axon guidance |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2018-08-01 |
description |
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. |
topic |
axon guidance chemotaxis growth cone gradient sensing shootin1 clutch |
url |
https://elifesciences.org/articles/34593 |
work_keys_str_mv |
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