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Validation of a Mouse Model to Disrupt LINC Complexes in a Cell-specific Manner
Published on: December 10, 2015
Mouse Disabled1 (DAB1) is a nucleocytoplasmic shuttling protein
Takao Honda1, Kazunori Nakajima
1Department of Anatomy, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
The Journal of Biological Chemistry
|October 26, 2006
Summary
Disabled1 (DAB1) protein, crucial for brain development, shuttles between the nucleus and cytoplasm. This finding suggests DAB1 may have nuclear functions beyond its known cytoplasmic roles in Reelin signaling.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Disabled1 (DAB1) is a key intracellular mediator of the Reelin-signaling pathway.
- DAB1 is essential for proper neuronal positioning during brain development.
- Previously, DAB1 was considered exclusively a cytoplasmic protein.
Purpose of the Study:
- To investigate the subcellular localization of DAB1.
- To determine if DAB1 undergoes nucleocytoplasmic shuttling.
- To identify the signals governing DAB1's nuclear import and export.
Main Methods:
- Treatment with leptomycin B, a CRM1 inhibitor, to assess nuclear export.
- Analysis of DAB1-EGFP fusion protein mutants to map localization signals.
- In vitro binding assays using purified recombinant proteins to study CRM1 interaction.
Main Results:
- DAB1 exhibits nucleocytoplasmic shuttling, accumulating in the nucleus upon CRM1 inhibition.
- A bipartite nuclear localization signal and two CRM1-dependent nuclear export signals were identified in DAB1.
- CRM1 directly binds to DAB1 in a RanGTP-dependent manner.
- Tyrosine phosphorylation of DAB1 does not alter its subcellular localization in vitro.
Conclusions:
- DAB1 is a nucleocytoplasmic shuttling protein.
- These findings suggest DAB1 may possess functional roles within the nucleus, in addition to its cytoplasmic functions.
- The identified localization signals provide insights into the regulation of DAB1 trafficking.
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