title: Doublecortin interacts with the ubiquitin protease DFFRX, which associates with microtubules in neuronal processes.
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 beta-catenin, preventing their degradation by the proteasome. Interestingly, unlike beta-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.
authors.affiliation: Laboratoire de Génétique et Physiopathologie des Retards Mentaux, GDPM, Institut Cochin, 75014 Paris, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Friocourt
authors.forename: Caroline
authors.initials: C
authors.lastname: Kappeler
authors.forename: Yoann
authors.initials: Y
authors.lastname: Saillour
authors.forename: Fabien
authors.initials: F
authors.lastname: Fauchereau
authors.forename: Manuel S
authors.initials: MS
authors.lastname: Rodriguez
authors.forename: Nadia
authors.initials: N
authors.lastname: Bahi
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Vinet
authors.forename: Philippe
authors.initials: P
authors.lastname: Chafey
authors.forename: Karine
authors.initials: K
authors.lastname: Poirier
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Taya
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Wood
authors.forename: Catherine
authors.initials: C
authors.lastname: Dargemont
authors.forename: Fiona
authors.initials: F
authors.lastname: Francis
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D019556:COS Cells; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D010447:Peptide Hydrolases / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D015534:Trans-Activators / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase; D015003:Yeasts; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; C000714328:DCX protein, human; C000714847:Dcx protein, mouse; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D015534:Trans-Activators; D014404:Tubulin; D025801:Ubiquitin; D051176:beta Catenin; D010450:Endopeptidases; D010447:Peptide Hydrolases; D043222:Ubiquitin Thiolesterase; C404328:Usp9x protein, mouse