Background Nitric oxide (NO) is a pleiotropic messenger molecule. and neuronal

Background Nitric oxide (NO) is a pleiotropic messenger molecule. and neuronal development. Major Conclusions Functional characterization of S-nitrosylated proteins that regulate neuronal development represents a rapidly emerging field. Recent studies uncover 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. [46 47 In addition dysregulation of MAP1B has been implicated in the pathogenesis of neurodevelopmental disorders including fragile X syndrome [48] spinocerebellar ataxia type 1 [49] and giant axonal neuropathy [50]. MAP1B has been reported to mediate nNOS-dependent axon retraction [51]. nNOS actually interacts with LC1 but not HC and cysteine-2457 on LC1 is usually S-nitrosylated (Fig. 3A). This S-nitrosylation reaction changes the conformation of LC1 and results in increased binding of the HC/LC1 MAP1B complex to microtubules. This leads to axonal retraction possibly by inhibiting the action of dynein which is necessary for axonal Rabbit polyclonal to ATS2. extension [51]. Fig. 3 S-Nitrosylation-mediated regulation of axonal retraction and adult neurogenesis. A) NO enhances refinement of axonal PP242 processes during brain development. S-Nitrosylation of MAP1B light chain (forming SNO-LC1) promotes binding to microtubules of the MAP1B … 3 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 PP242 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 PP242 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 day with an annual turnover rate of 1 1.75% in the human DG [54]. The newly-generated neurons differentiate into granule neurons and integrate into the existing hippocampal circuitry contributing to hippocampus-dependent learning and memory [52 53 Accumulating evidence shows that these new neurons play a pivotal role in fear conditioning [55] spatial and object recognition memory [56] and pattern separation [57]. Notably adult neurogenesis in the DG is usually affected in psychiatric and neurological disorders temporal lobe epilepsy [58] depressive disorder [59] bipolar disorder [60 61 schizophrenia [61-63] Huntington?痵 disease [54] and Alzheimer’s disease (AD) [64]. MEF2 is usually a member of the MADS (MCM1 Agamous Deficiens and Serum response factor) box superfamily of transcription factors [65]. Yeast and invertebrates such as and possess a single MEF2 while there are four isoforms MEF2A B C and D in vertebrates [65]. Our group originally cloned MEF2C and found it in the developing human brain [66]. The four MEF2 members are expressed in differential but overlapping expression patterns in both the temporal and spatial domains in developing and adult tissues. In general MEF2 expression is usually abundant in muscle lymphocytes and neurons [65]. The N-terminus consists of the MADS-box and MEF2 domains which are highly conserved across species and facilitate dimerization and DNA binding [65]. PP242 We as well as others have shown that MEF2 is usually involved in many different aspects of brain function from embryonic development to neuronal survival and synaptic plasticity. A neuronal function of MEF2 that was acknowledged early on involves its pro-survival activity [67 68 Excitotoxic insults or.