PUBLICATION

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

Authors
Weng, J.H., Liang, M.R., Chen, C.H., Tong, S.K., Huang, T.C., Lee, S.P., Chen, Y.R., Chen, C.T., and Chung, B.C.
ID
ZDB-PUB-130904-13
Date
2013
Source
Nature Chemical Biology   9(10): 636-42 (Journal)
Registered Authors
Chung, Bon-chu
Keywords
none
MeSH Terms
  • Cell Movement/drug effects*
  • Humans
  • Microtubule-Associated Proteins/agonists*
  • Microtubule-Associated Proteins/metabolism
  • Microtubules/drug effects*
  • Microtubules/metabolism
  • Neoplasm Proteins/agonists*
  • Neoplasm Proteins/metabolism
  • Polymerization/drug effects
  • Pregnenolone/chemistry
  • Pregnenolone/pharmacology*
  • Structure-Activity Relationship
PubMed
23955365 Full text @ Nat. Chem. Biol.
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 p150Glued 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.

Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Errata and Notes