ReferenceID 448
Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration
Nat Chem Biol
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 migr
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Record Fields
Scalar fields from the final reference record.
- Reference Id
- 448
- Evidence Id
- 17038
- Core Evidence Id
- 17038
- Source Reference Id
- 869
- Herb2 Reference Id
- HBREF001507
- Subject Paper Key
- HBIN040687_23955365
- Pubmed Id
- 23955365
- Doi
- 10.1038/nchembio.1321
- Paper Title
- Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration
- Paper 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.
- Journal
- Nat Chem Biol
- Publish Year
- 2013
- Experiment Subject
- zebrafish embryonic
- Experiment Type
- Animal Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration
- Bilingual Status
- semi_complete