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

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.
Mesh Terms:
Amino Acid Sequence, Animals, Cells, Cultured, Cytoplasm, Humans, Male, Molecular Sequence Data, Myelin Proteins, Nerve Regeneration, Nerve Tissue Proteins, Neurites, Neurons, Nuclear Proteins, PC12 Cells, Rats, Rats, Sprague-Dawley, Sequence Alignment, Two-Hybrid System Techniques
Mol. Cell. Neurosci.
Date: May. 01, 2009
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