Doublecortin interacts with the ubiquitin protease DFFRX, which associates with microtubules in neuronal processes

Date

2005

Authors

Friocourt, Gaelle
Kappeler, C.
Saillour, Y.
Fauchereau, Fabien
Rodriguez, M.S.
Bahi, Nadia
Vinet, Marie-Claude
Chafey, P.
Poirier, Karine
Taya, Shinichiro

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Journal article

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Molecular and Cellular Neuroscience, 2005; 28 (1):153-164

Statement of Responsibility

Gaëlle Friocourt, Caroline Kappeler, Yoann Saillour, Fabien Fauchereau, Manuel S. Rodriguez, Nadia Bahi, Marie-Claude Vinet, Philippe Chafey, Karine Poirier, Shinichiro Taya, Stephen A. Wood, Catherine Dargemont, Fiona Francis and Jamel Chelly

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Abstract

Doublecortin (DCX) is a microtubule-associated protein involved in neuronal migration, which causes X-linked lissencephaly and subcortical laminar heterotopia (SCLH) when mutated. Here we show that DCX interacts with the ubiquitin-specific protease Drosophila fat facets related on X chromosome (DFFRX). This interaction was confirmed by targeted mutagenesis, colocalization, and immunoprecipitation studies. DFFRX is thought to deubiquitinate specific substrates including β-catenin, preventing their degradation by the proteasome. Interestingly, unlike β-catenin, no ubiquitinated forms of DCX could be detected, and indeed we show that DCX interacts with a novel recognition domain in DFFRX, located outside of its catalytic site. We also show that DFFRX associates with microtubules at specific subcellular compartments, including those enriched in DCX. These results thus suggest that in addition to vesicular trafficking, DCX may play a role in the regulation of cell adhesion via its interaction with DFFRX in migrating and differentiating neurons.

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School of Molecular and Biomedical Science

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Copyright © 2004 Elsevier Inc. All rights reserved.

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