Translational Regulation of Acetylcholinesterase by the RNA-binding Protein Pumilio-2 at the Neuromuscular Synapse

Marrero, Emilio; Rossi, Susana G.; Darr, Andrew; Tsoulfas, Pantelis; Rotundo, Richard L.

doi:10.1074/jbc.m111.285510

Cited by 17 publications

(19 citation statements)

References 45 publications

(33 reference statements)

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“…The function of which, however, is unknown, as its complete absence causes no visible developmental abnormality. By contrast, Nanos' canonical partner, Pumilio, does function in the mammalian nervous system (Vessey et al, 2010;Marrero et al, 2011;Siemen et al, 2011). Because Nanos and Pumilio usually act in concert, the role of Nanos in the mammalian nervous system might have been overlooked, owing perhaps to the complexity of the mammalian nervous system.…”

Section: Discussionmentioning

confidence: 98%

Novel roles for Nanos in neural cell fate determination revealed by studies in a cnidarian

Kanska

Frank

2013

Journal of Cell Science

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SummaryNanos is a pan-metazoan germline marker, important for germ cell development and maintenance. In flies, Nanos also acts in posterior and neural development, but these functions have not been demonstrated experimentally in other animals. Using the cnidarian Hydractinia we have uncovered novel roles for Nanos in neural cell fate determination. Ectopic expression of Nanos2 increased the numbers of embryonic stinging cell progenitors, but decreased the numbers of neurons. Downregulation of Nanos2 had the opposite effect. Furthermore, Nanos2 blocked maturation of committed, post-mitotic nematoblasts. Hence, Nanos2 acts as a switch between two differentiation pathways, increasing the numbers of nematoblasts at the expense of neuroblasts, but preventing nematocyte maturation. Nanos2 ectopic expression also caused patterning defects, but these were not associated with deregulation of Wnt signaling, showing that the basic anterior-posterior polarity remained intact, and suggesting that numerical imbalance between nematocytes and neurons might have caused these defects, affecting axial patterning only indirectly. We propose that the functions of Nanos in germ cells and in neural development are evolutionarily conserved, but its role in posterior patterning is an insect or arthropod innovation.

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Section: Discussionmentioning

confidence: 98%

Novel roles for Nanos in neural cell fate determination revealed by studies in a cnidarian

Kanska

Frank

2013

Journal of Cell Science

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“…At 48 hours after transfection, the total RNA was extracted using Trizol (Invitrogen, Carlsbad, CA) according to manufacture’s instruction [31]. The extracted RNA was resolved in RNase-free water, and stored at −80°C for further uses.…”

Section: Methodsmentioning

confidence: 99%

HSCARG Inhibits NADPH Oxidase Activity through Regulation of the Expression of p47phox

et al. 2013

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Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase catalyzes the transfer of electrons from NADPH to O2, which is the main source of reactive oxygen species (ROS) in nonphagocytic cells. Excess ROS are toxic; therefore, keeping ROS in homeostasis in cells can protect cells from oxidative damage. It is meaningful to further understand the molecular mechanism by which ROS homeostasis is mediated. Human protein HSCARG is a newly identified oxidative sensor and a negative regulator of NF-κB. Here, we find that HSCARG represses the cellular ROS generation through inhibiting mRNA and protein expression of p47phox, a subunit of NADPH oxidase. In contrast, shRNA-mediated HSCARG knockdown increases endogenous p47phox expression level. And HSCARG has no obvious effect on ROS production in p47phox-depleted cells. Furthermore, HSCARG regulates p47phox through inhibition of NF-κB activity. Our findings identify HSCARG as a novel regulator in regulation of the activity of NADPH oxidase and ROS homeostasis.

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“…For over twenty years, Acetylcholinesterase is also involved to play other roles, in addition to its classical role of hydrolyzing Acetylcholine, i.e. in terminating synaptic transmission [4].…”

Section: Introductionmentioning

confidence: 99%

In Silico Study of miR-132 with mRNA of Acetylcholinesterase to Investigate the Binding Affinity for Interaction

Sohail¹

2018

J Mol Imag Dynamic

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Acetylcholinesterase (AChE) is a key enzyme in central nervous system which hydrolaze neurotransmitter acetylcholine (ACh) at cholinergic brain synapses. High expression of AChE in brain and muscles is responsible for diverse neurological conditions leading from neuromuscular, neurodegenerative and neuropsychological diseases. miRNA-132 is a non-coding RNA molecule which help to regulate the expression level of number of genes involved in neurological development, angiogenesis and synaptic transmission. However, miR-132 is the only miR so far that has been experimentally validated as targeting AChE, with consequences on inflammatory responses. Various bioinformatics tools like MODELLER, I-Tasser, ModeRNA, 3D-Dart, ERRAT, ProSA and Rampage were employed for AChE, miR-132 and mRNA model building and their validations. The binding affinities of these macromolecules were also investigated. The results revealed that the miR-132 binds to 3'-UTR region of AChE. The catalytic triad Ser-203, His-447 and Glu-334 found in active site gorge of protein binds to the ligand. Thus, the models of protein-ligand and mRNA-miR-132 complexes proved miR-132 as an inhibitor of Acetylcholinesterase. Therefore miR-132 can be a potent inhibitor for Acetylcholinesterase and further analysis of this inhibitor could be helpful for exploration of ligand binding pockets and designing of a novel therapeutic target to cure central nervous system disorders.

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Translational Regulation of Acetylcholinesterase by the RNA-binding Protein Pumilio-2 at the Neuromuscular Synapse

Cited by 17 publications

References 45 publications

Novel roles for Nanos in neural cell fate determination revealed by studies in a cnidarian

Novel roles for Nanos in neural cell fate determination revealed by studies in a cnidarian

HSCARG Inhibits NADPH Oxidase Activity through Regulation of the Expression of p47phox

In Silico Study of miR-132 with mRNA of Acetylcholinesterase to Investigate the Binding Affinity for Interaction

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