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

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dc.contributor.author Baba, Kentarou en
dc.contributor.author Yoshida, Wataru en
dc.contributor.author Toriyama, Michinori en
dc.contributor.author Shimada, Tadayuki en
dc.contributor.author Manning, Colleen F en
dc.contributor.author Saito, Michiko en
dc.contributor.author Kohno, Kenji en
dc.contributor.author Trimmer, James S en
dc.contributor.author Watanabe, Rikiya en
dc.contributor.author Inagaki, Naoyuki en
dc.contributor.author Kennedy, Tim en
dc.date.accessioned 2018-08-10T02:41:40Z en
dc.date.available 2018-08-10T02:41:40Z en
dc.date.issued 2018-08-07 en
dc.identifier.uri http://hdl.handle.net/10061/12561 en
dc.description.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. en
dc.language.iso en en
dc.publisher eLife Sciences Publications, Ltd en
dc.rights Baba et al. en
dc.subject axon guidance en
dc.subject chemotaxis en
dc.subject growth cone en
dc.subject gradient sensing en
dc.subject shootin1 en
dc.subject clutch en
dc.title Gradient-reading and mechano-effector machinery for netrin-1-induced axon guidance en
dc.type.nii Journal Article en
dc.contributor.transcription トリヤマ, ミチノリ ja
dc.contributor.transcription サイトウ, ミチコ ja
dc.contributor.transcription コウノ, ケンジ ja
dc.contributor.transcription イナガキ, ナオユキ ja
dc.contributor.alternative 鳥山, 道則 ja
dc.contributor.alternative 斉藤, 美知子 ja
dc.contributor.alternative 河野, 憲二 ja
dc.contributor.alternative 稲垣, 直之 ja
dc.textversion publisher en
dc.identifier.abstracturl https://doi.org/10.7554/eLife.34593.001 en
dc.identifier.jtitle eLife en
dc.identifier.volume 7 en
dc.relation.doi 10.7554/eLife.34593 en
dc.identifier.artnum e34593 en
dc.identifier.NAIST-ID 73293813 en
dc.identifier.NAIST-ID 73290512 en
dc.identifier.NAIST-ID 73290090 en
dc.identifier.NAIST-ID 73290314 en
dc.relation.pmid 30082022 en

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