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Publication : Nogo-A inhibits necdin-accelerated neurite outgrowth by retaining necdin in the cytoplasm.

First Author  Liu X Year  2009
Journal  Mol Cell Neurosci Volume  41
Issue  1 Pages  51-61
PubMed ID  19386232 Mgi Jnum  J:154259
Mgi Id  MGI:4367541 Doi  10.1016/j.mcn.2009.01.009
Citation  Liu X, et al. (2009) Nogo-A inhibits necdin-accelerated neurite outgrowth by retaining necdin in the cytoplasm. Mol Cell Neurosci 41(1):51-61
abstractText  Nogo-A has been identified in the central nervous system as an inhibitor for axonal regeneration. Previous works have mainly focused on Nogo-A in oligodendrocytes and the roles of neuronal intracellular Nogo-A remain elusive. To gain deep insight into the physiological functions of Nogo-A, a yeast two-hybrid screening was performed with Nogo-66 as bait. We identified a new interaction between Nogo-66 and necdin. Mutagenesis analysis revealed that the central region of necdin was indispensable for the interaction of necdin with Nogo-66. The interaction was further confirmed by co-immunoprecipitation in neural tissues and cultured cortical neurons. Morphological evidence showed that Nogo-A and necdin highly colocalized in rat cortical and dorsal root ganglia neurons. Ectopic expression of Nogo-A in HEK293 cells led to retention of necdin from the nucleus to the cytoplasm. Furthermore, overexpression of Nogo-A in PC12 cells and cultured cortical neurons inhibited necdin-accelerated neurite outgrowth. Meanwhile, necdin was found to be significantly sequestered in the cytoplasm of PC12 cells stably overexpressing Nogo-A. Together, these data suggest that Nogo-A is a novel necdin binding protein and inhibits necdin-accelerated neuronal neurite outgrowth by sequestering necdin in the cytoplasm.
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