Open AccessThe novel protein MANI modulates neurogenesis and neurite‐cone growth
Author(s) -
Mishra Manisha,
Akatsu Hiroyasu,
Heese Klaus
Publication year - 2011
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2010.01134.x
Subject(s) - neurite , microbiology and biotechnology , biology , growth cone , neural stem cell , neurogenesis , myelin , regeneration (biology) , immunoprecipitation , neurotrophin , neuroscience , axon , stem cell , receptor , central nervous system , cell culture , biochemistry , in vitro , genetics
Neuronal regeneration and axonal re‐growth in the injured mammalian central nervous system remains an unsolved field. 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]. In the present study we describe the novel protein MANI (myelin‐associated neurite‐outgrowth inhibitor) that localizes to neural membranes. Functional characterization of MANI overexpressing neural stem cells (NSCs) revealed that the protein promotes differentiation into catecholaminergic neurons. Yeast two‐hybrid screening and co‐immunoprecipitation experiments confirmed the cell division cycle protein 27 (Cdc27) as an interacting partner of Mani. The analyses of Mani‐overexpressing PC12 cells demonstrated that Mani retards neuronal axonal growth as a positive effector of Cdc27 expression and activity. 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.