The novel protein MANI modulates neurogenesis and neurite-cone growth

Abstract

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.

Livebearing or egg-laying mammals: 27 decisive nucleotides of FAM168

“…FAM168B is localized to neuronal cell membranes and has potential for inhibition of neurite-outgrowth and axonal guidance in the central nervous system (CNS). Our findings also suggested that FAM168B plays an important role in neuronal differentiation of neural stem cells (NSCs) into catecholaminergic neurons (17,18). Other studies have recently characterized the human FAM168A gene (also known as tongue cancer resistance-associated protein 1(TCRP1)) in oral squamous cell carcinoma (OSCC) cells (19)(20)(21).…”

“…Although the immune system is relatively undeveloped at birth and is developed during a lifetime of exposure to multiple foreign challenges (the so-called adaptive immune system), the development of the immune system, in particular innate immunity, starts early in fetal life for livebearing mammals (69)(70)(71). Considering this finding and our previous discoveries, the FAM168 gene family may contain crucial genes involved in the higher immune system and brain functions that are essential for mammals giving birth to live young (15,17,18,68).…”

“…Phylogenetic analyses based on coding sequences of these FAM168 genes revealed that they are paralogs and that the earliest emergence of these genes occurred in jawed vertebrates such as Callorhinchus milii. novel human neuronal protein, family with sequence similarity 168 member B (FAM168B also known as myelin-associated neurite-outgrowth inhibitor (MANI)), which is a member of the FAM168 family (17,18). FAM168B is localized to neuronal cell membranes and has potential for inhibition of neurite-outgrowth and axonal guidance in the central nervous system (CNS).…”

“…php?ID=9). Experimental data suggest that FAM168B (MANI) plays a role in neuro-axonal guidance and neuronal differentiation in the CNS (17,18), whereas FAM168A functions in chemoresistance by reducing cisplatin-mediated apoptosis (20,22). Thus, genetic differences between the FAM168A and FAM168B may explain why these two genes have distinct functions (2,56,59).…”

Brain-Site-Specific Proteome Changes Induced by Neuronal P60TRP Expression

“…from p60TRP transgenic mice [4] and control wild-type litter mates (C57BL/6J), were isolated after humane killing of the animals using approved anaesthetic methods. To analyse the tissue-specific protein expression, all efforts were made to minimize animal suffering and to reduce the number of animals used [4,5]. …”