Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration

Jui Hsia Weng, Ming Ren Liang, Chien Han Chen, Sok Keng Tong, Tzu Chiao Huang, Sue Ping Lee, Yet Ran Chen, Chao Tsen Chen, Bon Chu Chung

研究成果: Contribution to journalArticle査読

30 被引用数 (Scopus)

抄録

Pregnenolone (P5) is a neurosteroid that improves memory and neurological recovery. It is also required for zebrafish embryonic development. However, its mode of action is unclear. Here we show that P5 promotes cell migration and microtubule polymerization by binding a microtubule plus end-tracking protein, cytoplasmic linker protein 1 (CLIP-170). We captured CLIP-170 from zebrafish embryonic extract using a P5 photoaffinity probe conjugated to diaminobenzophenone. P5 interacted with CLIP-170 at its coiled-coil domain and changed it into an extended conformation. This increased CLIP-170 interaction with microtubules, dynactin subunit p150 Glued and LIS1; it also promoted CLIP-170-dependent microtubule polymerization. CLIP-170 was essential for P5 to promote microtubule abundance and zebrafish epiboly cell migration during embryogenesis, and overexpression of the P5-binding region of CLIP-170 delayed this migration. P5 also sustained migration directionality of cultured mammalian cells. Our results show that P5 activates CLIP-170 to promote microtubule polymerization and cell migration.

本文言語英語
ページ(範囲)636-642
ページ数7
ジャーナルNature Chemical Biology
9
10
DOI
出版ステータス出版済み - 10 2013
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 細胞生物学

フィンガープリント

「Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration」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