title: Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration.
abstract: 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.
authors: 1] Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan. [2] Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
authors: Jui-Hsia
authors: JH
authors: Weng
authors: Ming-Ren
authors: MR
authors: Liang
authors: Chien-Han
authors: CH
authors: Chen
authors: Sok-Keng
authors: SK
authors: Tong
authors: Tzu-Chiao
authors: TC
authors: Huang
authors: Sue-Ping
authors: SP
authors: Lee
authors: Yet-Ran
authors: YR
authors: Chen
authors: Chao-Tsen
authors: CT
authors: Chen
authors: Bon-Chu
authors: BC
authors: Chung
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000819:agonists* / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000819:agonists* / Q000378:metabolism; D058105:Polymerization / Q000187:drug effects; D011284:Pregnenolone / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C076744:cytoplasmic linker protein 170; D011284:Pregnenolone
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