NDLI: Processing and nuclear localization of CRMP2 during brain development induce neurite outgrowth inhibition.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Auger, Carole Becchi, Michel Rogemond, Véronique Giraudon, Pascale Belin, Marie-françoise Moradi-améli, Mahnaz Auvergnon, Nathalie Honnorat, Jérôme
Description	Author Affiliation: Rogemond V ( Inserm, U842, Université de Lyon, Lyon 1, UMR-S842, Lyon, France.)
Abstract	Collapsin response mediator proteins (CRMPs) are believed to play a crucial role in neuronal differentiation and axonal outgrowth. Among them, CRMP2 mediates axonal guidance by collapsing growth cones during development. This activity is correlated with the reorganization of cytoskeletal proteins. CRMP2 is implicated in the regulation of several intracellular signaling pathways. Two subtypes, A and B, and multiple cytosolic isoforms of CRMP2B with apparent masses between 62 and 66 kDa have previously been reported. Here, we show a new short isoform of 58 kDa, expressed during brain development, derived from C-terminal processing of the CRMP2B subtype. Although full-length CRMP2 is restricted to the cytoplasm, using transfection experiments, we demonstrate that a part of the short isoform is found in the nucleus. Interestingly, at the tissue level, this short CRMP2 is also found in a nuclear fraction of brain extract. By mutational analysis, we demonstrate, for the first time, that nuclear translocation occurs via nuclear localization signal (NLS) within residues Arg(471)-Lys(472) in CRMP2 sequence. The NLS may be unmasked after C-terminal processing; thereby, this motif may be surface-exposed. This short CRMP2 induces neurite outgrowth inhibition in neuroblastoma cells and suppressed axonal growth in cultured cortical neurons, whereas full-length CRMP2 promotes neurite elongation. The NLS-mutated short isoform, restricted to the cytoplasm, abrogates both neurite outgrowth and axon growth inhibition, indicating that short nuclear CRMP2 acts as a dominant signal. Therefore, post-transcriptional processing of CRMP2 together with its nuclear localization may be an important key in the regulation of neurite outgrowth in brain development.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	21
Volume Number	283
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2008-05-23
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Brain Growth & Development Metabolism Cell Differentiation Nerve Tissue Proteins Neurites Active Transport, Cell Nucleus Amino Acid Sequence Animals Cytology Gene Expression Regulation, Developmental Molecular Sequence Data Chemistry Genetics Protein Isoforms Protein Structure, Tertiary Receptor, EphA5 Sequence Alignment Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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