Apoptotic pathway and MAPKs differentially regulate chemotropic responses of retinal growth cones

Douglas Simon Campbell*, Christine E. Holt

*この研究の対応する著者

研究成果: Article査読

235 被引用数 (Scopus)

抄録

Previous work has shown that guidance cues trigger rapid changes in protein dynamics in retinal growth cones: netrin-1 stimulates both protein synthesis and degradation, while Sema3A elicits synthesis, and LPA induces degradation. What signaling pathways are involved? Our studies confirm that p42/44 MAPK mediates netrin-1 responses and further show that inhibiting its activity blocks cue-induced protein synthesis. Unexpectedly, p38 MAPK is also activated by netrin-1 in retinal growth cones and is required for chemotropic responses and translation. Sema3A- and LPA-induced responses, by contrast, require a single MAPK, p42/p44 and p38, respectively. In addition, we report that caspase-3, an apoptotic protease, is rapidly activated by netrin-1 and LPA in a proteasome- and p38-dependent manner and is required for chemotropic responses. These findings suggest that the apoptotic pathway may be used locally to control protein levels in growth cones and that the differential activation of MAPK pathways may underlie cue-directed migration.

本文言語English
ページ(範囲)939-952
ページ数14
ジャーナルNeuron
37
6
DOI
出版ステータスPublished - 2003 3 27
外部発表はい

ASJC Scopus subject areas

  • 神経科学(全般)

フィンガープリント

「Apoptotic pathway and MAPKs differentially regulate chemotropic responses of retinal growth cones」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル