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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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Qualitative Mani expression analysis in the crus cerebri, substantia nigra (sn) (near to the oculomotor neuron area) and the tegmentum of human brains. MANI protein expression in various brain areas (as indicated) obtained from control patients and PD patients, representative pictures are shown; a specific expression pattern within neuronal fibres (myelin sheets, arrows) could be observed (A). MANI protein expression in the sn area (around the oculomotor neuron area) under higher magnification (×10). Scale bar = 50 μm (B). MANI protein expression in select areas from (B, a, b, e, m) under higher magnification (×20 and ×60, respectively) (C–D).
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fig03: Qualitative Mani expression analysis in the crus cerebri, substantia nigra (sn) (near to the oculomotor neuron area) and the tegmentum of human brains. MANI protein expression in various brain areas (as indicated) obtained from control patients and PD patients, representative pictures are shown; a specific expression pattern within neuronal fibres (myelin sheets, arrows) could be observed (A). MANI protein expression in the sn area (around the oculomotor neuron area) under higher magnification (×10). Scale bar = 50 μm (B). MANI protein expression in select areas from (B, a, b, e, m) under higher magnification (×20 and ×60, respectively) (C–D).

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).


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

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

Qualitative Mani expression analysis in the crus cerebri, substantia nigra (sn) (near to the oculomotor neuron area) and the tegmentum of human brains. MANI protein expression in various brain areas (as indicated) obtained from control patients and PD patients, representative pictures are shown; a specific expression pattern within neuronal fibres (myelin sheets, arrows) could be observed (A). MANI protein expression in the sn area (around the oculomotor neuron area) under higher magnification (×10). Scale bar = 50 μm (B). MANI protein expression in select areas from (B, a, b, e, m) under higher magnification (×20 and ×60, respectively) (C–D).
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Related In: Results  -  Collection

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

fig03: Qualitative Mani expression analysis in the crus cerebri, substantia nigra (sn) (near to the oculomotor neuron area) and the tegmentum of human brains. MANI protein expression in various brain areas (as indicated) obtained from control patients and PD patients, representative pictures are shown; a specific expression pattern within neuronal fibres (myelin sheets, arrows) could be observed (A). MANI protein expression in the sn area (around the oculomotor neuron area) under higher magnification (×10). Scale bar = 50 μm (B). MANI protein expression in select areas from (B, a, b, e, m) under higher magnification (×20 and ×60, respectively) (C–D).
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).

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