Synaptic Plasticity Regulated by Protein–Protein Interactions and Posttranslational Modifications

2012 ◽  
pp. 1-43 ◽  
Author(s):  
Norihiko Yokoi ◽  
Masaki Fukata ◽  
Yuko Fukata
Keyword(s):  
Synaptic Plasticity ◽  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Protein Protein Interactions

scholarly journals The Role of Posttranslational Modifications in DNA Repair

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Miaomiao Bai ◽  
Dongdong Ti ◽  
Qian Mei ◽  
Jiejie Liu ◽  
Xin Yan ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Genome Stability ◽  
Protein Localization ◽  
Complex Structure ◽  
Protein Protein Interactions ◽  
Regulate Protein

The human body is a complex structure of cells, which are exposed to many types of stress. Cells must utilize various mechanisms to protect their DNA from damage caused by metabolic and external sources to maintain genomic integrity and homeostasis and to prevent the development of cancer. DNA damage inevitably occurs regardless of physiological or abnormal conditions. In response to DNA damage, signaling pathways are activated to repair the damaged DNA or to induce cell apoptosis. During the process, posttranslational modifications (PTMs) can be used to modulate enzymatic activities and regulate protein stability, protein localization, and protein-protein interactions. Thus, PTMs in DNA repair should be studied. In this review, we will focus on the current understanding of the phosphorylation, poly(ADP-ribosyl)ation, ubiquitination, SUMOylation, acetylation, and methylation of six typical PTMs and summarize PTMs of the key proteins in DNA repair, providing important insight into the role of PTMs in the maintenance of genome stability and contributing to reveal new and selective therapeutic approaches to target cancers.

scholarly journals Group I Metabotropic Glutamate Receptors and Interacting Partners: An Update

2022 ◽  
Vol 23 (2) ◽  
pp. 840
Author(s):  
Li-Min Mao ◽  
Alaya Bodepudi ◽  
Xiang-Ping Chu ◽  
John Q. Wang
Keyword(s):  
Synaptic Plasticity ◽  
Protein Interactions ◽  
Metabotropic Glutamate Receptors ◽  
Adaptor Proteins ◽  
Mammalian Brain ◽  
Amino Acid Residues ◽  
Protein Protein Interactions ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Associated Proteins

Group I metabotropic glutamate (mGlu) receptors (mGlu1/5 subtypes) are G protein-coupled receptors and are broadly expressed in the mammalian brain. These receptors play key roles in the modulation of normal glutamatergic transmission and synaptic plasticity, and abnormal mGlu1/5 signaling is linked to the pathogenesis and symptomatology of various mental and neurological disorders. Group I mGlu receptors are noticeably regulated via a mechanism involving dynamic protein–protein interactions. Several synaptic protein kinases were recently found to directly bind to the intracellular domains of mGlu1/5 receptors and phosphorylate the receptors at distinct amino acid residues. A variety of scaffolding and adaptor proteins also interact with mGlu1/5. Constitutive or activity-dependent interactions between mGlu1/5 and their interacting partners modulate trafficking, anchoring, and expression of the receptors. The mGlu1/5-associated proteins also finetune the efficacy of mGlu1/5 postreceptor signaling and mGlu1/5-mediated synaptic plasticity. This review analyzes the data from recent studies and provides an update on the biochemical and physiological properties of a set of proteins or molecules that interact with and thus regulate mGlu1/5 receptors.

scholarly journals Chemical toolbox for ‘live’ biochemistry to understand enzymatic functions in living systems

2019 ◽  
Author(s):  
Toru Komatsu ◽  
Yasuteru Urano
Keyword(s):  
Environmental Factors ◽  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Live Cell ◽  
Living Systems ◽  
Protein Protein Interactions ◽  
Redox States ◽  
Recent Advances ◽  
Protein Functions ◽  
Research Tools

Abstract In this review, we present an overview of the recent advances in chemical toolboxes that are used to provide insights into ‘live’ protein functions in living systems. Protein functions are mediated by various factors inside of cells, such as protein−protein interactions, posttranslational modifications, and they are also subject to environmental factors such as pH, redox states and crowding conditions. Obtaining a true understanding of protein functions in living systems is therefore a considerably difficult task. Recent advances in research tools have allowed us to consider ‘live’ biochemistry as a valid approach to precisely understand how proteins function in a live cell context.

scholarly journals Intrinsic Disorder in Tetratricopeptide Repeat Proteins

2020 ◽  
Vol 21 (10) ◽  
pp. 3709 ◽  
Author(s):  
Nathan W. Van Bibber ◽  
Cornelia Haerle ◽  
Roy Khalife ◽  
Bin Xue ◽  
Vladimir N. Uversky
Keyword(s):  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Tandem Repeats ◽  
Intrinsically Disordered Protein ◽  
Intrinsic Disorder ◽  
Protein Protein Interactions ◽  
Systematic Analysis ◽  
Tetratricopeptide Repeats ◽  
Intrinsically Disordered ◽  
Tetratricopeptide Repeat Proteins

Among the realm of repeat containing proteins that commonly serve as “scaffolds” promoting protein-protein interactions, there is a family of proteins containing between 2 and 20 tetratricopeptide repeats (TPRs), which are functional motifs consisting of 34 amino acids. The most distinguishing feature of TPR domains is their ability to stack continuously one upon the other, with these stacked repeats being able to affect interaction with binding partners either sequentially or in combination. It is known that many repeat-containing proteins are characterized by high levels of intrinsic disorder, and that many protein tandem repeats can be intrinsically disordered. Furthermore, it seems that TPR-containing proteins share many characteristics with hybrid proteins containing ordered domains and intrinsically disordered protein regions. However, there has not been a systematic analysis of the intrinsic disorder status of TPR proteins. To fill this gap, we analyzed 166 human TPR proteins to determine the degree to which proteins containing TPR motifs are affected by intrinsic disorder. Our analysis revealed that these proteins are characterized by different levels of intrinsic disorder and contain functional disordered regions that are utilized for protein-protein interactions and often serve as targets of various posttranslational modifications.

scholarly journals PathwayMatcher: proteoform-centric network construction enables fine-granularity multiomics pathway mapping

GigaScience ◽  
2019 ◽  
Vol 8 (8) ◽  
Author(s):  
Luis Francisco Hernández Sánchez ◽  
Bram Burger ◽  
Carlos Horro ◽  
Antonio Fabregat ◽  
Stefan Johansson ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Knowledge Bases ◽  
Protein Isoforms ◽  
Biomedical Data ◽  
Protein Protein Interactions ◽  
Gene Sets ◽  
Functional Knowledge ◽  
Pathway Analyses ◽  
Different Levels

Abstract Background Mapping biomedical data to functional knowledge is an essential task in bioinformatics and can be achieved by querying identifiers (e.g., gene sets) in pathway knowledge bases. However, the isoform and posttranslational modification states of proteins are lost when converting input and pathways into gene-centric lists. Findings Based on the Reactome knowledge base, we built a network of protein-protein interactions accounting for the documented isoform and modification statuses of proteins. We then implemented a command line application called PathwayMatcher (github.com/PathwayAnalysisPlatform/PathwayMatcher) to query this network. PathwayMatcher supports multiple types of omics data as input and outputs the possibly affected biochemical reactions, subnetworks, and pathways. Conclusions PathwayMatcher enables refining the network representation of pathways by including proteoforms defined as protein isoforms with posttranslational modifications. The specificity of pathway analyses is hence adapted to different levels of granularity, and it becomes possible to distinguish interactions between different forms of the same protein.

scholarly journals Distinct p53 acetylation cassettes differentially influence gene-expression patterns and cell fate

2006 ◽  
Vol 173 (4) ◽  
pp. 533-544 ◽  
Author(s):  
Chad D. Knights ◽  
Jason Catania ◽  
Simone Di Giovanni ◽  
Selen Muratoglu ◽  
Ricardo Perez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Biological Activities ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
P53 Gene ◽  
Protein Protein Interactions

The activity of the p53 gene product is regulated by a plethora of posttranslational modifications. An open question is whether such posttranslational changes act redundantly or dependently upon one another. We show that a functional interference between specific acetylated and phosphorylated residues of p53 influences cell fate. Acetylation of lysine 320 (K320) prevents phosphorylation of crucial serines in the NH2-terminal region of p53; only allows activation of genes containing high-affinity p53 binding sites, such as p21/WAF; and promotes cell survival after DNA damage. In contrast, acetylation of K373 leads to hyperphosphorylation of p53 NH2-terminal residues and enhances the interaction with promoters for which p53 possesses low DNA binding affinity, such as those contained in proapoptotic genes, leading to cell death. Further, acetylation of each of these two lysine clusters differentially regulates the interaction of p53 with coactivators and corepressors and produces distinct gene-expression profiles. By analogy with the “histone code” hypothesis, we propose that the multiple biological activities of p53 are orchestrated and deciphered by different “p53 cassettes,” each containing combination patterns of posttranslational modifications and protein–protein interactions.

scholarly journals GluR2 protein-protein interactions and the regulation of AMPA receptors during synaptic plasticity

2003 ◽  
Vol 358 (1432) ◽  
pp. 715-720 ◽  
Author(s):  
Fabrice Duprat ◽  
Michael Daw ◽  
Wonil Lim ◽  
Graham Collingridge ◽  
John Isaac
Keyword(s):  
Synaptic Plasticity ◽  
Ampa Receptor ◽  
Protein Interactions ◽  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Synaptic Proteins ◽  
Mammalian Brain ◽  
Protein Protein Interactions ◽  
Term Potentiation

AMPA-type glutamate receptors mediate most fast excitatory synaptic transmissions in the mammalian brain. They are critically involved in the expression of long-term potentiation and long-term depression, forms of synaptic plasticity that are thought to underlie learning and memory. A number of synaptic proteins have been identified that interact with the intracellular C-termini of AMPA receptor subunits. Here, we review recent studies and present new experimental data on the roles of these interacting proteins in regulating the AMPA receptor function during basal synaptic transmission and plasticity.

Quantitative Imaging of FRET-Based Biosensors for Cell- and Organelle-Specific Analyses in Plants

2016 ◽  
Vol 22 (2) ◽  
pp. 300-310 ◽  
Author(s):  
Swayoma Banerjee ◽  
Luis Rene Garcia ◽  
Wayne K. Versaw
Keyword(s):  
High Precision ◽  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Dynamic Range ◽  
Quantitative Imaging ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
High Dynamic Range ◽  
Imaging Data ◽  
Protein Protein Interactions

AbstractGenetically encoded Förster resonance energy transfer (FRET)-based biosensors have been used to report relative concentrations of ions and small molecules, as well as changes in protein conformation, posttranslational modifications, and protein–protein interactions. Changes in FRET are typically quantified through ratiometric analysis of fluorescence intensities. Here we describe methods to evaluate ratiometric imaging data acquired through confocal microscopy of a FRET-based inorganic phosphate biosensor in different cells and subcellular compartments of Arabidopsis thaliana. Linear regression was applied to donor, acceptor, and FRET-derived acceptor fluorescence intensities obtained from images of multiple plants to estimate FRET ratios and associated location-specific spectral correction factors with high precision. FRET/donor ratios provided a combination of high dynamic range and precision for this biosensor when applied to the cytosol of both root and leaf cells, but lower precision when this ratiometric method was applied to chloroplasts. We attribute this effect to quenching of donor fluorescence because high precision was achieved with FRET/acceptor ratios and thus is the preferred ratiometric method for this organelle. A ligand-insensitive biosensor was also used to distinguish nonspecific changes in FRET ratios. These studies provide a useful guide for conducting quantitative ratiometric studies in live plants that is applicable to any FRET-based biosensor.

Plant cell microcompartments: a redox-signaling perspective

2013 ◽  
Vol 394 (2) ◽  
pp. 203-216 ◽  
Author(s):  
Sabine Zachgo ◽  
Guy T. Hanke ◽  
Renate Scheibe
Keyword(s):  
Information Flow ◽  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Stress Responses ◽  
Protein Concentration ◽  
Redox State ◽  
Cellular Protein ◽  
Functional Modules ◽  
Protein Protein Interactions ◽  
Dynamic Nature

Abstract This review describes how transient protein-protein interactions can contribute to direct information flow between subsequent steps of metabolic and signaling pathways, focusing on the redox perspective. Posttranslational modifications are often the basis for the dynamic nature of such macromolecular aggregates, named microcompartments. The high cellular protein concentration promotes these interactions that are prone to disappear upon the extraction of proteins from cells. Changes of signaling molecules, such as metabolites, effectors or phytohormones, or the redox state in the cellular microenvironment, can modulate them. The signaling network can, therefore, respond in a very flexible and appropriate manner, such that metabolism, stress responses, and developmental steps are integrated by multiple and changing contacts between functional modules. This allows plants to survive and persist by continuously and flexibly adapting to a challenging or even adverse environment.

scholarly journals Intracellular Cleavage of the Cx43 C-Terminal Domain by Matrix-Metalloproteases: A Novel Contributor to Inflammation?

2015 ◽  
Vol 2015 ◽  
pp. 1-18 ◽  
Author(s):  
Marijke De Bock ◽  
Nan Wang ◽  
Elke Decrock ◽  
Geert Bultynck ◽  
Luc Leybaert
Keyword(s):  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Tissue Injury ◽  
Matrix Metalloproteases ◽  
Matrix Remodeling ◽  
Protein Protein Interactions ◽  
Channel Function ◽  
Terminal Domain ◽  
Direct Cell ◽  
Electric Signals

The coordination of tissue function is mediated by gap junctions (GJs) that enable direct cell-cell transfer of metabolic and electric signals. GJs are formed by connexin (Cx) proteins of which Cx43 is most widespread in the human body. Beyond its role in direct intercellular communication, Cx43 also forms nonjunctional hemichannels (HCs) in the plasma membrane that mediate the release of paracrine signaling molecules in the extracellular environment. Both HC and GJ channel function are regulated by protein-protein interactions and posttranslational modifications that predominantly take place in the C-terminal domain of Cx43. Matrix metalloproteases (MMPs) are a major group of zinc-dependent proteases, known to regulate not only extracellular matrix remodeling, but also processing of intracellular proteins. Together with Cx43 channels, both GJs and HCs, MMPs contribute to acute inflammation and a small number of studies reports on an MMP-Cx43 link. Here, we build further on these reports and present a novel hypothesis that describes proteolytic cleavage of the Cx43 C-terminal domain by MMPs and explores possibilities of how such cleavage events may affect Cx43 channel function. Finally, we set out how aberrant channel function resulting from cleavage can contribute to the acute inflammatory response during tissue injury.

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