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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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Mani protein expression analysis in various tissues. Tissue obtained from an adult mouse. Specific high expression was observed in the brain with a major band at ∼40 kD representing glycosylated Mani (A). Expression of Mani protein in various transfected (Mani)/non-transfected cell lines and brain tissue. NSC: mock/GFP-transfected NSCs, NSC-Mani: Mani-transfected NSCs, NSC-diff: NSCs differentiated in neurobasal medium (NB) supplemented with B27 without Egf (mainly glia cells), ES: embryonic stem cells, N2a: mouse neuroblastoma cell line, PC12: mock/GFP-transfected PC12 cells, PC12-Mani: Mani-transfected PC12 cells, HEK: human embryonic kidney cell line, CG4: glia-progenitor cell line, HeLa: human cervical tumour cell line, Cx: mouse brain cortex tissue lysate, Hp: mouse brain hippocampus tissue lysate. Only the brain-tissue lysate shows the lower band at ∼20 kD – compare with Fig. S4 (B).
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fig02: Mani protein expression analysis in various tissues. Tissue obtained from an adult mouse. Specific high expression was observed in the brain with a major band at ∼40 kD representing glycosylated Mani (A). Expression of Mani protein in various transfected (Mani)/non-transfected cell lines and brain tissue. NSC: mock/GFP-transfected NSCs, NSC-Mani: Mani-transfected NSCs, NSC-diff: NSCs differentiated in neurobasal medium (NB) supplemented with B27 without Egf (mainly glia cells), ES: embryonic stem cells, N2a: mouse neuroblastoma cell line, PC12: mock/GFP-transfected PC12 cells, PC12-Mani: Mani-transfected PC12 cells, HEK: human embryonic kidney cell line, CG4: glia-progenitor cell line, HeLa: human cervical tumour cell line, Cx: mouse brain cortex tissue lysate, Hp: mouse brain hippocampus tissue lysate. Only the brain-tissue lysate shows the lower band at ∼20 kD – compare with Fig. S4 (B).

Mentions: A rabbit polyclonal anti-MANI antibody was raised and purified against aa89–aa102; however, it may not detect FAM168A (family with sequence similarity 168, member A) because 4 aa are different in this region (Fig. S1; BioGenes GmbH, Berlin, Germany). Antibody specificity was tested using recombinantly expressed MANI in Escherichia coli (not shown) as well as in mammalian cell lines overexpressing Mani or a Mani-GFP fusion protein (Figs 2 and S2).


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

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

Mani protein expression analysis in various tissues. Tissue obtained from an adult mouse. Specific high expression was observed in the brain with a major band at ∼40 kD representing glycosylated Mani (A). Expression of Mani protein in various transfected (Mani)/non-transfected cell lines and brain tissue. NSC: mock/GFP-transfected NSCs, NSC-Mani: Mani-transfected NSCs, NSC-diff: NSCs differentiated in neurobasal medium (NB) supplemented with B27 without Egf (mainly glia cells), ES: embryonic stem cells, N2a: mouse neuroblastoma cell line, PC12: mock/GFP-transfected PC12 cells, PC12-Mani: Mani-transfected PC12 cells, HEK: human embryonic kidney cell line, CG4: glia-progenitor cell line, HeLa: human cervical tumour cell line, Cx: mouse brain cortex tissue lysate, Hp: mouse brain hippocampus tissue lysate. Only the brain-tissue lysate shows the lower band at ∼20 kD – compare with Fig. S4 (B).
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Related In: Results  -  Collection

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fig02: Mani protein expression analysis in various tissues. Tissue obtained from an adult mouse. Specific high expression was observed in the brain with a major band at ∼40 kD representing glycosylated Mani (A). Expression of Mani protein in various transfected (Mani)/non-transfected cell lines and brain tissue. NSC: mock/GFP-transfected NSCs, NSC-Mani: Mani-transfected NSCs, NSC-diff: NSCs differentiated in neurobasal medium (NB) supplemented with B27 without Egf (mainly glia cells), ES: embryonic stem cells, N2a: mouse neuroblastoma cell line, PC12: mock/GFP-transfected PC12 cells, PC12-Mani: Mani-transfected PC12 cells, HEK: human embryonic kidney cell line, CG4: glia-progenitor cell line, HeLa: human cervical tumour cell line, Cx: mouse brain cortex tissue lysate, Hp: mouse brain hippocampus tissue lysate. Only the brain-tissue lysate shows the lower band at ∼20 kD – compare with Fig. S4 (B).
Mentions: A rabbit polyclonal anti-MANI antibody was raised and purified against aa89–aa102; however, it may not detect FAM168A (family with sequence similarity 168, member A) because 4 aa are different in this region (Fig. S1; BioGenes GmbH, Berlin, Germany). Antibody specificity was tested using recombinantly expressed MANI in Escherichia coli (not shown) as well as in mammalian cell lines overexpressing Mani or a Mani-GFP fusion protein (Figs 2 and S2).

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