Mouse disabled1 (DAB1) is a nucleocytoplasmic shuttling protein

Takao Honda, Kazunori Nakajima

研究成果: Article査読

32 被引用数 (Scopus)

抄録

Disabled1 (DAB1) is an intracellular mediator of the Reelin-signaling pathway and essential for correct neuronal positioning during brain development. So far, DAB1 has been considered a cytoplasmic protein. Here, we show that DAB1 is subject to nucleocytoplasmic shuttling. In its steady state, DAB1 is mainly located in the cytoplasm. However, treatment with leptomycine B, a specific inhibitor of the CRM1 (chromosomal region maintenance 1)-RanGTP-dependent nuclear export, resulted in nuclear accumulation of DAB1. By using deletion or substitutional mutants of DAB1 fused with enhanced green fluorescent protein, we have mapped a bipartite nuclear localization signal and two CRM1-dependent nuclear export signals. These targeting signals were functional in both Neuro2a cells and primary cerebral cortical neurons. Using purified recombinant proteins, we have shown thatCRM1binds to DAB1 directly in a RanGTP-dependent manner.Wealso show that tyrosine phosphorylation of DAB1, which is indispensable for the layer formation of the brain, by Fyn tyrosine kinase or Reelin stimulation did not affect the subcellular localization of DAB1 in vitro. These results suggest that DAB1 is a nucleocytoplasmic shuttling protein and raise the possibility that DAB1 plays a role in the nucleus as well as in the cytoplasm.

本文言語English
ページ(範囲)38951-38965
ページ数15
ジャーナルJournal of Biological Chemistry
281
50
DOI
出版ステータスPublished - 2006 12 15

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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