Doublecortin interacts with the ubiquitin protease DFFRX, which associates with microtubules in neuronal processes.
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.
Friocourt
Gaëlle
G
Laboratoire de Génétique et Physiopathologie des Retards Mentaux, GDPM, Institut Cochin, 75014 Paris, France.
Kappeler
Caroline
C
Saillour
Yoann
Y
Fauchereau
Fabien
F
Rodriguez
Manuel S
MS
Bahi
Nadia
N
Vinet
Marie-Claude
MC
Chafey
Philippe
P
Poirier
Karine
K
Taya
Shinichiro
S
Wood
Stephen A
SA
Dargemont
Catherine
C
Francis
Fiona
F
Chelly
Jamel
J
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
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