The novel protein MANI modulates neurogenesis and neurite-cone growth.
Bottom Line: To date, three myelin-associated proteins [Nogo or reticulon 4 (RTN4), myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMG)] are known to inhibit axonal regeneration via activation of the neuronal glycosylphosphatidylinositol-anchored Nogo receptor [NgR, together with p75 neurotrophin receptor (p75NTR) and Lingo-1].We show that knockdown of Cdc27, a component of the anaphase-promoting complex (APC), leads to enhanced neurite outgrowth.Our finding describes the novel MANI-Cdc27-APC pathway as an important cascade that prevents neurons from extending axons, thus providing implications for the potential treatment of neurodegenerative diseases.
Affiliation: Department of Molecular and Cell Biology, School of Biological Sciences, College of Science, Nanyang Technological University, Singapore.Show MeSH
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Mentions: Because we originally found the MANI mRNA to be down-regulated in AD brains, in a cDNA subtraction analysis , we reconfirmed this finding by RT-PCR and IHC in human patients and observed a significant reduction of MANI mRNA levels in AD patients. Protein expression analysis in human brains disclosed (though no obvious down-regulation) that MANI was present within (neuronal) axonal fibres and to be associated with myelin sheets (Fig. 1A–D; Fig. S2 [antibody specificity analysis] and Table S1). Because of our limited access to human tissue, we confirmed the down-regulation of Mani at protein levels in AD using an AD mouse model (Fig. 1E).
Affiliation: Department of Molecular and Cell Biology, School of Biological Sciences, College of Science, Nanyang Technological University, Singapore.