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The novel protein MANI modulates neurogenesis and neurite-cone growth.

Mishra M, Akatsu H, Heese K - J. Cell. Mol. Med. (2011)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cell Biology, School of Biological Sciences, College of Science, Nanyang Technological University, Singapore.

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Related in: MedlinePlus

Mani mediates neuronal survival. Effect of Mani expression on the survival of PC12 cells. Upper panel: Western blot analysis of Mani expression, which was down-regulated via application of the siRNA method. Lower panel: analysis using the ELISA-Cell-Titre 96® AQueous assay as described under ‘Materials and methods’ (Supplementary Information). Data represent mean ± S.D. of four independent experiments, each performed in duplicates (*P < 0.05 compared with controls [mock/GFP transfected]) (A). Mani-overexpressing cells demonstrated higher levels of phosphorylated Bcl2 at Ser70 but decreased phosphorylation at Thr56, even without Ngf stimulation indicating Mani’s anti-apoptotic function [23]. Cells were grown and stimulated as indicated for 6 days with 100 ng/ml Ngf. Controls (C) were mock/GFP-transfected cells (B).
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fig06: Mani mediates neuronal survival. Effect of Mani expression on the survival of PC12 cells. Upper panel: Western blot analysis of Mani expression, which was down-regulated via application of the siRNA method. Lower panel: analysis using the ELISA-Cell-Titre 96® AQueous assay as described under ‘Materials and methods’ (Supplementary Information). Data represent mean ± S.D. of four independent experiments, each performed in duplicates (*P < 0.05 compared with controls [mock/GFP transfected]) (A). Mani-overexpressing cells demonstrated higher levels of phosphorylated Bcl2 at Ser70 but decreased phosphorylation at Thr56, even without Ngf stimulation indicating Mani’s anti-apoptotic function [23]. Cells were grown and stimulated as indicated for 6 days with 100 ng/ml Ngf. Controls (C) were mock/GFP-transfected cells (B).

Mentions: To further unravel the function of Mani, it was knocked down by the siRNA technology and a significant reduction in cell survival was observed (Fig. 6A). We also examined the expression level of survival-related proteins and found that Mani-transfected cells have significantly increased levels of activated Bcl2, which again confirmed that Mani functions as a survival-promoting protein (Fig. 6B).


The novel protein MANI modulates neurogenesis and neurite-cone growth.

Mishra M, Akatsu H, Heese K - J. Cell. Mol. Med. (2011)

Mani mediates neuronal survival. Effect of Mani expression on the survival of PC12 cells. Upper panel: Western blot analysis of Mani expression, which was down-regulated via application of the siRNA method. Lower panel: analysis using the ELISA-Cell-Titre 96® AQueous assay as described under ‘Materials and methods’ (Supplementary Information). Data represent mean ± S.D. of four independent experiments, each performed in duplicates (*P < 0.05 compared with controls [mock/GFP transfected]) (A). Mani-overexpressing cells demonstrated higher levels of phosphorylated Bcl2 at Ser70 but decreased phosphorylation at Thr56, even without Ngf stimulation indicating Mani’s anti-apoptotic function [23]. Cells were grown and stimulated as indicated for 6 days with 100 ng/ml Ngf. Controls (C) were mock/GFP-transfected cells (B).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4373362&req=5

fig06: Mani mediates neuronal survival. Effect of Mani expression on the survival of PC12 cells. Upper panel: Western blot analysis of Mani expression, which was down-regulated via application of the siRNA method. Lower panel: analysis using the ELISA-Cell-Titre 96® AQueous assay as described under ‘Materials and methods’ (Supplementary Information). Data represent mean ± S.D. of four independent experiments, each performed in duplicates (*P < 0.05 compared with controls [mock/GFP transfected]) (A). Mani-overexpressing cells demonstrated higher levels of phosphorylated Bcl2 at Ser70 but decreased phosphorylation at Thr56, even without Ngf stimulation indicating Mani’s anti-apoptotic function [23]. Cells were grown and stimulated as indicated for 6 days with 100 ng/ml Ngf. Controls (C) were mock/GFP-transfected cells (B).
Mentions: To further unravel the function of Mani, it was knocked down by the siRNA technology and a significant reduction in cell survival was observed (Fig. 6A). We also examined the expression level of survival-related proteins and found that Mani-transfected cells have significantly increased levels of activated Bcl2, which again confirmed that Mani functions as a survival-promoting protein (Fig. 6B).

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cell Biology, School of Biological Sciences, College of Science, Nanyang Technological University, Singapore.

Show MeSH
Related in: MedlinePlus