scholarly journals Stress-induced changes in the S-palmitoylation and S-nitrosylation of synaptic proteins

2018 ◽  
Author(s):  
Monika Zareba-Koziol ◽  
Anna Bartkowiak-Kaczmarek ◽  
Izabela Figiel ◽  
Adam Krzystyniak ◽  
Tomasz Wojtowicz ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Posttranslational Modifications ◽  
Network Connectivity ◽  
Covalent Modification ◽  
Stress Disorders ◽  
Synaptic Proteins ◽  
Postsynaptic Density Proteins ◽  
Reversible Covalent ◽  
As Stress ◽  
Induced Changes

SummaryThe precise regulation of synaptic integrity is critical for neuronal network connectivity and proper brain function. Essential aspects of the activity and localization of synaptic proteins are regulated by posttranslational modifications. S-palmitoylation is a reversible covalent modification of the cysteine with palmitate. It modulates affinity of the protein for cell membranes and membranous compartments. Intracellular palmitoylation dynamics are regulated by other posttranslational modifications, such as S-nitrosylation. Still unclear, however, are the ways in which this crosstalk is affected in brain pathology, such as stress-related disorders. Using a newly developed mass spectrometry-based approach (Palmitoylation And Nitrosylation Interplay Monitoring), we analyzed the endogenous S-palmitoylation and S-nitrosylation of postsynaptic density proteins at the level of specific single cysteines in a mouse model of chronic stress. Our results suggest that atypical mechanism of crosstalk between the S-palmitoylation and S-nitrosylation of synaptic proteins might be one of the major events associated with chronic stress disorders.

scholarly journals Stress-induced Changes in the S-palmitoylation and S-nitrosylation of Synaptic Proteins

2019 ◽  
Vol 18 (10) ◽  
pp. 1916-1938 ◽  
Author(s):  
Monika Zareba-Koziol ◽  
Anna Bartkowiak-Kaczmarek ◽  
Izabela Figiel ◽  
Adam Krzystyniak ◽  
Tomasz Wojtowicz ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Posttranslational Modifications ◽  
Protein Localization ◽  
Network Connectivity ◽  
Covalent Modification ◽  
Synaptic Proteins ◽  
Postsynaptic Density Proteins ◽  
Protein Functions ◽  
Reversible Covalent ◽  
As Stress

The precise regulation of synaptic integrity is critical for neuronal network connectivity and proper brain function. Essential aspects of the activity and localization of synaptic proteins are regulated by posttranslational modifications. S-palmitoylation is a reversible covalent modification of the cysteine with palmitate. It modulates affinity of the protein for cell membranes and membranous compartments. Intracellular palmitoylation dynamics are regulated by crosstalk with other posttranslational modifications, such as S-nitrosylation. S-nitrosylation is a covalent modification of cysteine thiol by nitric oxide and can modulate protein functions. Therefore, simultaneous identification of endogenous site-specific proteomes of both cysteine modifications under certain biological conditions offers new insights into the regulation of functional pathways. Still unclear, however, are the ways in which this crosstalk is affected in brain pathology, such as stress-related disorders. Using a newly developed mass spectrometry-based approach Palmitoylation And Nitrosylation Interplay Monitoring (PANIMoni), we analyzed the endogenous S-palmitoylation and S-nitrosylation of postsynaptic density proteins at the level of specific single cysteine in a mouse model of chronic stress. Among a total of 813 S-PALM and 620 S-NO cysteine sites that were characterized on 465 and 360 proteins, respectively, we sought to identify those that were differentially affected by stress. Our data show involvement of S-palmitoylation and S-nitrosylation crosstalk in the regulation of 122 proteins including receptors, scaffolding proteins, regulatory proteins and cytoskeletal components. Our results suggest that atypical crosstalk between the S-palmitoylation and S-nitrosylation interplay of proteins involved in synaptic transmission, protein localization and regulation of synaptic plasticity might be one of the main events associated with chronic stress disorder, leading to destabilization in synaptic networks.

scholarly journals Chronic Stress-Induced Changes in Pro-Inflammatory Cytokines and Spinal Glia Markers in the Rat: A Time Course Study

2012 ◽  
Vol 19 (6) ◽  
pp. 367-376 ◽  
Author(s):  
Viktoriya Golovatscka ◽  
Helena Ennes ◽  
Emeran A. Mayer ◽  
Sylvie Bradesi
Keyword(s):  
Chronic Stress ◽  
Inflammatory Cytokines ◽  
Time Course ◽  
Time Course Study ◽  
Induced Changes ◽  
Pro Inflammatory Cytokines

Epigenetic regulation of genes in learning and memory

2010 ◽  
Vol 48 ◽  
pp. 263-274 ◽  
Author(s):  
Tania L. Roth ◽  
Eric D. Roth ◽  
J. David Sweatt
Keyword(s):  
Learning And Memory ◽  
Cognitive Dysfunction ◽  
Epigenetic Regulation ◽  
Memory Formation ◽  
Covalent Modification ◽  
Gene Activity ◽  
Neural Function ◽  
Post Translational Modifications ◽  
Novel Approach ◽  
Induced Changes

Rapid advances in the field of epigenetics are revealing a new way to understand how we can form and store strong memories of significant events in our lives. Epigenetic modifications of chromatin, namely the post-translational modifications of nuclear proteins and covalent modification of DNA that regulate gene activity in the CNS (central nervous system), continue to be recognized for their pivotal role in synaptic plasticity and memory formation. At the same time, studies are correlating aberrant epigenetic regulation of gene activity with cognitive dysfunction prevalent in CNS disorders and disease. Epigenetic research, then, offers not only a novel approach to understanding the molecular transcriptional mechanisms underlying experience-induced changes in neural function and behaviour, but potential therapeutic treatments aimed at alleviating cognitive dysfunction. In this chapter, we discuss data regarding epigenetic marking of genes in adult learning and memory formation and impairment thereof, as well as data showcasing the promise for manipulating the epigenome in restoring memory capacity.

scholarly journals SerThr-PhosphoProteome of Brain from Aged PINK1-KO+A53T-SNCA Mice Reveals pT1928-MAP1B and pS3781-ANK2 Deficits, as Hub between Autophagy and Synapse Changes

2019 ◽  
Vol 20 (13) ◽  
pp. 3284 ◽  
Author(s):  
Georg Auburger ◽  
Suzana Gispert ◽  
Sylvia Torres-Odio ◽  
Marina Jendrach ◽  
Nadine Brehm ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Alpha Synuclein ◽  
Synaptic Function ◽  
Label Free ◽  
Similar Reduction ◽  
C2 Domains ◽  
Brain Hemispheres ◽  
Locomotor Deficits ◽  
As Stress ◽  
Transmission Factors

Hereditary Parkinson’s disease (PD) can be triggered by an autosomal dominant overdose of alpha-Synuclein (SNCA) as stressor or the autosomal recessive deficiency of PINK1 Serine/Threonine-phosphorylation activity as stress-response. We demonstrated the combination of PINK1-knockout with overexpression of SNCAA53T in double mutant (DM) mice to exacerbate locomotor deficits and to reduce lifespan. To survey posttranslational modifications of proteins underlying the pathology, brain hemispheres of old DM mice underwent quantitative label-free global proteomic mass spectrometry, focused on Ser/Thr-phosphorylations. As an exceptionally strong effect, we detected >300-fold reductions of phosphoThr1928 in MAP1B, a microtubule-associated protein, and a similar reduction of phosphoSer3781 in ANK2, an interactor of microtubules. MAP1B depletion is known to trigger perturbations of microtubular mitochondria trafficking, neurite extension, and synaptic function, so it was noteworthy that relevantly decreased phosphorylation was also detected for other microtubule and microfilament factors, namely MAP2S1801, MARK1S394, MAP1AT1794, KIF1AS1537, 4.1NS541, 4.1GS86, and ADD2S528. While the MAP1B heavy chain supports regeneration and growth cones, its light chain assists DAPK1-mediated autophagy. Interestingly, relevant phosphorylation decreases of DAPK2S299, VPS13DS2429, and VPS13CS2480 in the DM brain affected regulators of autophagy, which are implicated in PD. Overall, significant downregulations were enriched for PFAM C2 domains, other kinases, and synaptic transmission factors upon automated bioinformatics, while upregulations were not enriched for selective motifs or pathways. Validation experiments confirmed the change of LC3 processing as reflection of excessive autophagy in DM brain, and dependence of ANK2/MAP1B expression on PINK1 levels. Our new data provide independent confirmation in a mouse model with combined PARK1/PARK4/PARK6 pathology that MAP1B/ANK2 phosphorylation events are implicated in Parkinsonian neurodegeneration. These findings expand on previous observations in Drosophila melanogaster that the MAP1B ortholog futsch in the presynapse is a primary target of the PARK8 protein LRRK2, and on a report that MAP1B is a component of the pathological Lewy body aggregates in PD patient brains. Similarly, ANK2 gene locus variants are associated with the risk of PD, ANK2 interacts with PINK1/Parkin-target proteins such as MIRO1 or ATP1A2, and ANK2-derived peptides are potent inhibitors of autophagy.

scholarly journals Role of the modulation of Nkb pathway in chronic stress induced changes in the BNST and consequences on the anxiety behavior

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S78
Author(s):  
Aurelie Menigoz ◽  
Donald Rainnie ◽  
Katie Barrett ◽  
Megan Jiang ◽  
Larry Young
Keyword(s):  
Chronic Stress ◽  
Anxiety Behavior ◽  
Induced Changes

scholarly journals Chronic Stress in Adolescents and Its Neurobiological and Psychopathological Consequences: An RDoC Perspective

2017 ◽  
Vol 1 ◽  
pp. 247054701771564 ◽  
Author(s):  
Chandni Sheth ◽  
Erin McGlade ◽  
Deborah Yurgelun-Todd
Keyword(s):  
Psychiatric Disorders ◽  
Chronic Stress ◽  
Neural Circuits ◽  
Environmental Influence ◽  
Research Domain Criteria ◽  
Psychiatric Illnesses ◽  
Orthogonal Dimension ◽  
Induced Changes ◽  
Behavioral Constructs ◽  
Research Domain

The Research Domain Criteria (RDoC) initiative provides a strategy for classifying psychopathology based on behavioral dimensions and neurobiological measures. Neurodevelopment is an orthogonal dimension in the current RDoC framework; however, it has not yet been fully incorporated into the RDoC approach. A combination of both a neurodevelopmental and RDoC approach offers a multidimensional perspective for understanding the emergence of psychopathology during development. Environmental influence (e.g., stress) has a profound impact on the risk for development of psychiatric illnesses. It has been shown that chronic stress interacts with the developing brain, producing significant changes in neural circuits that eventually increase the susceptibility for development of psychiatric disorders. This review highlights effects of chronic stress on the adolescent brain, as adolescence is a period characterized by a combination of significant brain alterations, high levels of stress, and emergence of psychopathology. The literature synthesized in this review suggests that chronic stress-induced changes in neurobiology and behavioral constructs underlie the shared vulnerability across a number of disorders in adolescence. The review particularly focuses on depression and substance use disorders; however, a similar argument can also be made for other psychopathologies, including anxiety disorders. The summarized findings underscore the need for a framework to integrate neurobiological findings from disparate psychiatric disorders and to target transdiagnostic mechanisms across disorders.

Cigarette smoke affects posttranslational modifications and inhibits capacitation-induced changes in human sperm proteins

2014 ◽  
Vol 43 ◽  
pp. 125-129 ◽  
Author(s):  
Vibha Shrivastava ◽  
Hannah Marmor ◽  
Sholom Chernyak ◽  
Marc Goldstein ◽  
Miriam Feliciano ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Posttranslational Modifications ◽  
Human Sperm ◽  
Sperm Proteins ◽  
Induced Changes
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