S-Nitrosylation in neurogenesis and neuronal development

doi:10.1016/j.bbagen.2014.12.013

Biochimica et Biophysica Acta (BBA) - General Subjects

Volume 1850, Issue 8, August 2015, Pages 1588-1593

https://doi.org/10.1016/j.bbagen.2014.12.013 Get rights and content

Highlights

•
S-Nitrosylation networks modulate neuronal differentiation and development.
•
S-Nitrosylated GAPDH/Siah/CREB cascade controls dendritic growth.
•
S-Nitrosylation of MAP1B regulates axonal retraction
•
S-Nitrosylation of MEF2 serves as a negative switch for adult neurogenesis.

Abstract

Background

Nitric oxide (NO) is a pleiotropic messenger molecule. The multidimensional actions of NO species are, in part, mediated by their redox nature. Oxidative posttranslational modification of cysteine residues to regulate protein function, termed S-nitrosylation, constitutes a major form of redox-based signaling by NO.

Scope of review

S-Nitrosylation directly modifies a number of cytoplasmic and nuclear proteins in neurons. S-Nitrosylation modulates neuronal development by reaction with specific proteins, including the transcription factor MEF2. This review focuses on the impact of S-nitrosylation on neurogenesis and neuronal development.

Major conclusions

Functional characterization of S-nitrosylated proteins that regulate neuronal development represents a rapidly emerging field. Recent studies reveal that S-nitrosylation-mediated redox signaling plays an important role in several biological processes essential for neuronal differentiation and maturation.

General significance

Investigation of S-nitrosylation in the nervous system has elucidated new molecular and cellular mechanisms for neuronal development. S-Nitrosylated proteins in signaling networks modulate key events in brain development. Dysregulation of this redox-signaling pathway may contribute to neurodevelopmental disabilities such as autism spectrum disorder (ASD). Thus, further elucidation of the involvement of S-nitrosylation in brain development may offer potential therapeutic avenues for neurodevelopmental disorders.

This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation.

Section snippets

Redox signaling by S-nitrosylation

NO was first identified as an Endothelium Derived Relaxing Factor (EDRF) [1], but also serves as a more widespread signaling molecule [2]. NO-mediated physiological processes include vasodilation, immune function, neurotransmission, and neuronal maturation [2], [3], [4], [5], [6]. Three types of NO synthases generate endogenous NO in mammalian cells: neuronal NOS (nNOS, NOS1); inducible NOS (iNOS, NOS2); and endothelial NOS (eNOS, NOS3) [2], [7], [8]. All three NOS isoforms are expressed in the

CREB (cyclic-AMP response element binding protein)-dependent dendritic growth and nitrosylation pathways

Dendrites are branched extensions from neurons that receive afferent inputs. The molecular and cellular mechanisms underlying dendritic development have been a focus of research for the past several decades. Recent studies revealed that dendritic development is regulated in both a neuronal activity-dependent and -independent manner [15], [16]. Both signaling pathways ultimately lead to activation of transcription factors such as the nuclear effector CREB (cAMP response element-binding protein).

Microtubule-associated protein 1B (MAP1B) and S-nitrosylation in axonal retraction

An axon is the neuronal process that serves to relay afferent signals via action potential propagation. Axonal guidance, outgrowth, and retraction are coordinated by dynamic rearrangements of the actin and microtubule cytoskeletons. The coordinated remodeling of the cytoskeleton is essential for brain development. Missense and splice-site mutations in α- and β-tubulin isotypes, constituents of neuronal microtubules, cause human neurodevelopmental disorders such as lissencephaly [39].

S-Nitrosylated myocyte enhancer factor 2 (MEF2) in adult neurogenesis

Active neurogenesis continues throughout life in the adult brain of mammals, including humans [52], [53]. Adult neurogenesis is not observed throughout the brain, however, but is mainly restricted to two distinct areas: the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone of the hippocampal dentate gyrus (DG) [52], [53]. A recent study assessed the presence of nuclear bomb-test derived ¹⁴C in genomic DNA and calculated that approximately 700 neurons are added every

Perspectives for the future

Emerging evidence suggests the significance of redox-signaling networks, in large measure mediated by S-nitrosylation. Here, we discuss the importance of these reactions in neurogenesis and neuronal development. Analysis of individual proteins has revealed that S-nitrosylation reactions regulate the activity (either inhibition or activation) of specific proteins; alternatively, S-nitrosylation can affect the binding of one protein to another in a complex. For example, the SNO-GAPDH/SNO-HDAC2

Acknowledgments

S.-i.O. was supported by a Shiley-Marcos Alzheimer's Disease Research Center (UCSD) Pilot Award and NIH grant R21 MH102672. S.A.L. was supported in part by NIH grants R01 NS086890, R01 ES017462, R21 NS080799, P01 HD29587, P01 ES016738, and P30 NS076411, and awards from the Michael J. Fox Foundation, the California Institute for Regenerative Medicine (CIRM TR4-06788), and the Brain & Behavior Research Foundation. We thank Sarah Moore and Scott R. McKercher for critical comments on this

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Citation Excerpt :
Consequently, BDNF-mediated SNO of HDAC2 plays a role in dendritic development [32,34]. Rearrangement of actin and myosin in cytoskeletons is necessary for axonal growth, axonal guidance, axonal modification and brain development [20] and these processes are also mediated by NO [35]. Furthermore, SNO of microtubule-associated protein B1 (MAPB1) leads to a modification of axon retraction [36].
Nitric oxide (NO) is a multifunctional signalling molecule and a neurotransmitter that plays an important role in physiological and pathophysiological processes. In physiological conditions, NO regulates cell survival, differentiation and proliferation of neurons. It also regulates synaptic activity, plasticity and vesicle trafficking. NO affects cellular signalling through protein S-nitrosylation, the NO-mediated posttranslational modification of cysteine thiols (SNO). SNO can affect protein activity, protein-protein interaction and protein localization. Numerous studies have shown that excessive NO and SNO can lead to nitrosative stress in the nervous system, contributing to neuropathology. In this review, we summarize the role of NO and SNO in the progression of neurodevelopmental, psychiatric and neurodegenerative disorders, with special attention to autism spectrum disorder (ASD). We provide mechanistic insights into the contribution of NO in diverse brain disorders. Finally, we suggest that pharmacological agents that can inhibit or augment the production of NO as well as new approaches to modulate the formation of SNO-proteins can serve as a promising approach for the treatment of diverse brain disorders.

View all citing articles on Scopus

^☆: This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation.

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ReviewS-Nitrosylation in neurogenesis and neuronal development☆

Highlights

Abstract

Background

Scope of review

Major conclusions

General significance

Section snippets

Redox signaling by S-nitrosylation

CREB (cyclic-AMP response element binding protein)-dependent dendritic growth and nitrosylation pathways

Microtubule-associated protein 1B (MAP1B) and S-nitrosylation in axonal retraction

S-Nitrosylated myocyte enhancer factor 2 (MEF2) in adult neurogenesis

Perspectives for the future

Acknowledgments

Neuron

Trends Mol. Med.

Trends Mol. Med.

Trends Neurosci.

Biochem. Pharmacol.

Nitric Oxide

Mol. Cell

Cell Calcium

Neuron

Curr. Opin. Neurobiol.

Mol. Cell

Neuron

Biochim. Biophys. Acta

Biochim. Biophys. Acta

Trends Genet.

Curr. Opin. Genet. Dev.

Trends Biochem. Sci.

Cell

J. Biol. Chem.

Biochim. Biophys. Acta

Cell

Cell

Cell Rep.

Cell

Curr. Opin. Chem. Biol.

Biochim. Biophys. Acta

Biochim. Biophys. Acta

Free Radic. Biol. Med.

Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta

J. Pharmacol. Exp. Ther.

Protein S-nitrosylation: purview and parameters

Nat. Rev. Mol. Cell Biol.

Nitric oxide synthases: structure, function and inhibition

Biochem. J.

S-Nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death

Science

Export by red blood cells of nitric oxide bioactivity

Nature

Thioredoxin catalyzes the S-nitrosation of the caspase-3 active site cysteine

Nat. Chem. Biol.

Protein denitrosylation: enzymatic mechanisms and cellular functions

Nat. Rev. Mol. Cell Biol.

Nuclear calcium signaling

Adv. Exp. Med. Biol.

Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene

Nature

Calcium regulation of neuronal gene expression

Proc. Natl. Acad. Sci. U. S. A.

Trk receptors: roles in neuronal signal transduction

Annu. Rev. Biochem.

Glutamate and neurotrophic factors in neuronal plasticity and disease

Ann. N.Y. Acad. Sci.

S-Nitrosylation of histone deacetylase 2 induces chromatin remodelling in neurons

Nature

S-Nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding

Nat. Cell Biol.

GAPDH mediates nitrosylation of nuclear proteins

Nat. Cell Biol.

Neurotrophin-mediated degradation of histone methyltransferase by S-nitrosylation cascade regulates neuronal differentiation

Proc. Natl. Acad. Sci. U. S. A.

Glyceraldehyde-3-phosphate dehydrogenase: nuclear translocation participates in neuronal and nonneuronal cell death

Proc. Natl. Acad. Sci. U. S. A.

Regulated protein denitrosylation by cytosolic and mitochondrial thioredoxins

Science

Review
S-Nitrosylation in neurogenesis and neuronal development☆