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
Related in: MedlinePlus
Mentions: For additional functional investigations of Mani, we continued our studies with NSCs (E14) (Fig. 5). As shown in (Fig. 5B), Mani-transfected neurospheres continuously cultured in the presence of Egf (epidermal growth factor) demonstrated a moderate change in Gfap (glial fibrillary acidic protein, a glial cell marker) expression, but evidently higher expression levels of the neuronal marker Tubb3 (neuron-specific β-class-III tubulin, Tuj1). Additionally, the stem cell marker Nestin was significantly reduced, indicating that Mani drives NSCs towards neurogenesis, even in the presence of the mitogen Egf (Fig. 5B). The increase in Tubb3 in Mani-transfected NSCs led us to the identification of the differentiating neuronal subtype. Therefore, we proceeded to check the expression levels of various neuronal markers, such as Chat (choline acetyltransferase, marker for cholinergic neurons), Gad (glutamate decarboxylase, marker for GABAergic neurons) and Th (marker for catecholaminergic neurons). Of utmost interest is our finding that Mani induced a striking up-regulation of Th (Fig. 5B) correlating with our findings of high expression of Mani in the catecholaminergic PC12 cells and Th+ areas in the CNS (Figs 2, 4, S6 and S7). In contrast, other neuro-specific markers, such as Chat or Gad (data not shown), remained unchanged.
Affiliation: Department of Molecular and Cell Biology, School of Biological Sciences, College of Science, Nanyang Technological University, Singapore.