Nogo-A inhibits necdin-accelerated neurite outgrowth by retaining necdin in the cytoplasm
| Autor: | Xiao-Hui Xu, Michio Niinobe, Yonggang Wang, Cheng He, Chang-Lin Lu, Xiujie Liu, Kazuaki Yoshikawa, Yong Zhang, Wei Zhu |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Cytoplasm Neurite Nogo Proteins Molecular Sequence Data Central nervous system Nerve Tissue Proteins Biology PC12 Cells Rats Sprague-Dawley Cellular and Molecular Neuroscience Two-Hybrid System Techniques mental disorders Neurites medicine Animals Humans Amino Acid Sequence Molecular Biology Cells Cultured Neurons Binding protein HEK 293 cells Nuclear Proteins Cell Biology Nerve Regeneration Rats Cell biology medicine.anatomical_structure Ectopic expression Sequence Alignment Neuroscience Nucleus Myelin Proteins psychological phenomena and processes Intracellular |
| Zdroj: | Molecular and Cellular Neuroscience. 41:51-61 |
| ISSN: | 1044-7431 |
| DOI: | 10.1016/j.mcn.2009.01.009 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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