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: In lieu of our observation of higher Mani expression in the catecholaminergic (tyrosine hydroxylase-positive [Th+]) PC12 cells and in line with the gene database (NCBI) indicating that the mouse sequence of Mani is expressed in the thalamus as well as in dopaminergic neurons of the substantia nigra (sn), we investigated the expression of MANI in the brains of human patients with PD (Table S2). Surprisingly, we detected MANI only in neuronal fibres near the sn; in fact, IHC indicated a strong staining of the myelin sheets, suggesting that MANI is expressed specifically in myelinated neurons (Fig. 3).
Affiliation: Department of Molecular and Cell Biology, School of Biological Sciences, College of Science, Nanyang Technological University, Singapore.