scholarly journals The Role of the Proteasome in Platelet Function

2021 ◽  
Vol 22 (8) ◽  
pp. 3999
Author(s):  
Abed El-Hakim El-Kadiry ◽  
Yahye Merhi
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
De Novo ◽  
Functional Coupling ◽  
Platelet Activity ◽  
Vascular Integrity ◽  
Primary Hemostasis ◽  
Limited Protein ◽  
And Function

Platelets are megakaryocyte-derived acellular fragments prepped to maintain primary hemostasis and thrombosis by preserving vascular integrity. Although they lack nuclei, platelets harbor functional genomic mediators that bolster platelet activity in a signal-specific manner by performing limited de novo protein synthesis. Furthermore, despite their limited protein synthesis, platelets are equipped with multiple protein degradation mechanisms, such as the proteasome. In nucleated cells, the functions of the proteasome are well established and primarily include proteostasis among a myriad of other signaling processes. However, the role of proteasome-mediated protein degradation in platelets remains elusive. In this review article, we recapitulate the developing literature on the functions of the proteasome in platelets, discussing its emerging regulatory role in platelet viability and function and highlighting how its functional coupling with the transcription factor NF-κB constitutes a novel potential therapeutic target in atherothrombotic diseases.

scholarly journals Learning Naturalistic Temporal Structure in the Posterior Medial Network

2018 ◽  
Vol 30 (9) ◽  
pp. 1345-1365 ◽  
Author(s):  
Mariam Aly ◽  
Janice Chen ◽  
Nicholas B. Turk-Browne ◽  
Uri Hasson
Keyword(s):  
De Novo ◽  
Temporal Structure ◽  
Temporal Integration ◽  
Functional Coupling ◽  
Relative Role ◽  
Dynamics And Function ◽  
And Function ◽  
The Brain ◽  
Event Schemas

The posterior medial network is at the apex of a temporal integration hierarchy in the brain, integrating information over many seconds of viewing intact, but not scrambled, movies. This has been interpreted as an effect of temporal structure. Such structure in movies depends on preexisting event schemas, but temporal structure can also arise de novo from learning. Here, we examined the relative role of schema-consistent temporal structure and arbitrary but consistent temporal structure on the human posterior medial network. We tested whether, with repeated viewing, the network becomes engaged by scrambled movies with temporal structure. Replicating prior studies, activity in posterior medial regions was immediately locked to stimulus structure upon exposure to intact, but not scrambled, movies. However, for temporally structured scrambled movies, functional coupling within the network increased across stimulus repetitions, rising to the level of intact movies. Thus, temporal structure is a key determinant of network dynamics and function in the posterior medial network.

scholarly journals Learning naturalistic temporal structure in the posterior medial network

2017 ◽  
Author(s):  
Mariam Aly ◽  
Janice Chen ◽  
Nicholas B. Turk-Browne ◽  
Uri Hasson
Keyword(s):  
De Novo ◽  
Temporal Structure ◽  
Temporal Integration ◽  
Functional Coupling ◽  
Relative Role ◽  
Dynamics And Function ◽  
And Function ◽  
The Brain ◽  
Event Schemas

AbstractThe posterior medial network is at the apex of a temporal integration hierarchy in the brain, integrating information over many seconds of viewing intact, but not scrambled, movies. This has been interpreted as an effect of temporal structure. Such structure in movies depends on pre-existing event schemas, but temporal structure can also arise de novo from learning. Here we examined the relative role of schema-consistent temporal structure and arbitrary but consistent temporal structure on the human posterior medial network. We tested whether, with repeated viewing, the network becomes engaged by scrambled movies with temporal structure. Replicating prior studies, posterior medial regions were immediately locked to stimulus structure upon exposure to intact but not scrambled movies. However, for temporally structured scrambled movies, functional coupling within the network increased across stimulus repetitions, rising to the level of intact movies. Thus, temporal structure is a key determinant of network dynamics and function.

The possible role of protein degradation in altered membrane structure and function

1984 ◽  
Vol 5 (4) ◽  
pp. 343-346
Author(s):  
Joseph M. Rifkind ◽  
Jin Tsai Wang ◽  
Joy G. Mohanty ◽  
George S. Roth
Keyword(s):  
Protein Degradation ◽  
Membrane Structure ◽  
Structure And Function ◽  
Membrane Structure And Function ◽  
And Function

Memory Reorganization by Synaptic Protein Degradation

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
B.-K. Kaang
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Memory Retrieval ◽  
De Novo ◽  
Critical Role ◽  
Contextual Fear Conditioning ◽  
Synaptic Proteins ◽  
Protein Synthesis Inhibitor ◽  
Synaptic Protein

An accumulating body of evidence shows that the retrieval process of long-term memory is not static and requires de novo protein synthesis. Thus long-term memories are dynamic and particularly become fragile during its retrieval. Importantly, memory retrieval is regarded as a step necessary for incorporating new information into preexisting memories. We have examined whether protein degradation is involved in the memory reorganization or not. In this presentation I will present the evidence that synaptic proteins are degraded by polyubiquitination and proteasome pathway in the hippocampus after the retrieval of contextual fear conditioning. In addition, we found that the infusion of a proteasome inhibitor into the hippocampus prevented the memory impairment induced by anisomycin, a protein synthesis inhibitor. This indicates that ubiquitin/proteasome-dependent protein degradation is involved in destabilization processes accompanying the memory retrieval. It also supports our hypothesis that preexisting memory is disrupted by synaptic protein degradation before updated memory is strengthened by protein synthesis. Our data also showed that synaptic protein degradation plays a critical role in fear memory extinction, a simple form of memory reorganization. Taken together, synaptic protein degradation is critically involved in the reorganization of the preexisting memories.

Renal arginine and protein synthesis are increased during early endotoxemia in mice

2002 ◽  
Vol 282 (2) ◽  
pp. F316-F323 ◽  
Author(s):  
Marcella M. Hallemeesch ◽  
Peter B. Soeters ◽  
Nicolaas E. P. Deutz
Keyword(s):  
Nitric Oxide ◽  
Protein Synthesis ◽  
Protein Metabolism ◽  
De Novo ◽  
Early Response ◽  
No Production ◽  
Arginine Metabolism ◽  
First Time ◽  
Adaptive Role

The kidney has an important function in arginine metabolism, because the kidney is the main endogenous source for de novo arginine production from circulating citrulline. In conditions such as sepsis, nitric oxide (NO) production is increased and is dependent on extracellular arginine availability. To elucidate the adaptive role of renal de novo arginine synthesis in a condition of increased NO production, we studied renal arginine metabolism in a mouse model of endotoxemia. Because arginine flux is largely dependent on protein flux, we also measured protein metabolism in mice. Female mice were injected intraperitoneally with lipopolysaccharide; control mice received 0.9% NaCl. Six hours later, renal blood flow was measured with the use of para-aminohippuric acid. Arginine and protein metabolism were studied using organ-balance, stable-isotope techniques. Systemic NO production was increased in the endotoxin-treated mice. In addition, renal protein synthesis and de novo arginine production from citrulline were increased. However, no effect on renal NO production was observed. In conclusion, increased renal de novo arginine production may serve to sustain systemic NO production. To our knowledge, it was shown for the first time that renal protein synthesis is enhanced in the early response to endotoxemia.

scholarly journals Skin Basement Membrane: The Foundation of Epidermal Integrity—BM Functions and Diverse Roles of Bridging Molecules Nidogen and Perlecan

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Dirk Breitkreutz ◽  
Isabell Koxholt ◽  
Kathrin Thiemann ◽  
Roswitha Nischt
Keyword(s):  
Basement Membrane ◽  
De Novo ◽  
Molecular Assembly ◽  
Specific Gene ◽  
Stage Of Development ◽  
Molecular Aspects ◽  
And Function ◽  
Molecular Adaptors ◽  
Nidogen 1

The epidermis functions in skin as first defense line or barrier against environmental impacts, resting on extracellular matrix (ECM) of the dermis underneath. Both compartments are connected by the basement membrane (BM), composed of a set of distinct glycoproteins and proteoglycans. Herein we are reviewing molecular aspects of BM structure, composition, and function regarding not only (i) the dermoepidermal interface but also (ii) the resident microvasculature, primarily focusing on theper senonscaffold forming components perlecan and nidogen-1 and nidogen-2. Depletion or functional deficiencies of any BM component are lethal at some stage of development or around birth, though BM defects vary between organs and tissues. Lethality problems were overcome by developmental stage- and skin-specific gene targeting or by cell grafting and organotypic (3D) cocultures of normal or defective cells, which allows recapitulating BM formationde novo. Thus, evidence is accumulating that BM assembly and turnover rely on mechanical properties and composition of the adjacent ECM and the dynamics of molecular assembly, including further “minor” local components, nidogens largely functioning as catalysts or molecular adaptors and perlecan as bridging stabilizer. Collectively, orchestration of BM assembly, remodeling, and the role of individual players herein are determined by the developmental, tissue-specific, or functional context.

scholarly journals Analysis of M4 Transmembrane Segments in NMDA Receptor Function: A Negative Allosteric Modulatory Site at the GluN1 M4 is Determining the Efficiency of Neurosteroid Modulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Kai Langer ◽  
Adriana Müller-Längle ◽  
Jannik Wempe ◽  
Bodo Laube
Keyword(s):  
Nmda Receptor ◽  
Crucial Role ◽  
Surface Expression ◽  
Functional Coupling ◽  
Receptor Function ◽  
Transmembrane Segments ◽  
The Core ◽  
And Function ◽  
Receptor Assembly

Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated ion channels that play a crucial role in excitatory synaptic transmission in the central nervous system. Each subunit contributes with three helical transmembrane segments (M1, M3, and M4) and a pore loop (M2) to form the channel pore. Recent studies suggest that the architecture of all eukaryotic iGluRs derives from a common prokaryotic ancestral receptor that lacks M4 and consists only of transmembrane segments M1 and M3. Although significant contribution has emerged in the last years, the role of this additionally evolved transmembrane segment in iGluR assembly and function remains unclear. Here, we have investigated how deletions and mutations of M4 in members of the NMDA receptor (NMDAR) subfamily, the conventional heteromeric GluN1/GluN2 and glycine-gated GluN1/GluN3 NMDARs, affect expression and function in Xenopus oocytes. We show that deletion of M4 in the GluN1, GluN2A, or GluN3A subunit, despite retained receptor assembly and cell surface expression, results in nonfunctional membrane receptors. Coexpression of the corresponding M4 as an isolated peptide in M4-deleted receptors rescued receptor function of GluN1/GluN2A NMDARs without altering the apparent affinity of glutamate or glycine. Electrophysiological analyses of agonist-induced receptor function and its modulation by the neurosteroid pregnenolone sulfate (PS) at mutations of the GluN1-M4/GluN2/3-transmembrane interfaces indicate a crucial role of position M813 in M4 of GluN1 for functional coupling to the core receptor and the negative modulatory effects of PS. Substitution of residues and insertion of interhelical disulfide bridges confirmed interhelical interactions of positions in M4 of GluN1 with residues of transmembrane segments of neighboring subunits. Our results show that although M4s in NMDARs are not important for receptor assembly and surface expression, the residues at the subunit interface are substantially involved in M4 recognition of the core receptor and regulation of PS efficacy. Because mutations in the M4 of GluN1 specifically resulted in loss of PS-induced inhibition of GluN1/GluN2A and GluN1/GluN3A NMDAR currents, our results point to distinct roles of M4s in NMDAR modulation and highlight the importance of the evolutionarily newly evolved M4 for selective in vivo modulation of glutamate- and glycine-activated NMDARs by steroids.

scholarly journals The morphogenetic role of midline mesendoderm and ectoderm in the development of the forebrain and the midbrain of the mouse embryo

Development ◽  
2000 ◽  
Vol 127 (9) ◽  
pp. 1799-1813 ◽  
Author(s):  
A. Camus ◽  
B.P. Davidson ◽  
S. Billiards ◽  
P. Khoo ◽  
J.A. Rivera-Perez ◽  
...  
Keyword(s):  
Neural Tube ◽  
Mouse Embryo ◽  
De Novo ◽  
Gene Activity ◽  
Anteroposterior Patterning ◽  
De Novo Gene ◽  
Ventral Neural Tube ◽  
And Function ◽  
The Impact

The anterior midline tissue (AML) of the late gastrula mouse embryo comprises the axial mesendoderm and the ventral neuroectoderm of the prospective forebrain, midbrain and rostral hindbrain. In this study, we have investigated the morphogenetic role of defined segments of the AML by testing their inductive and patterning activity and by assessing the impact of their ablation on the patterning of the neural tube at the early-somite-stage. Both rostral and caudal segments of the AML were found to induce neural gene activity in the host tissue; however, the de novo gene activity did not show any regional characteristic that might be correlated with the segmental origin of the AML. Removal of the rostral AML that contains the prechordal plate resulted in a truncation of the head accompanied by the loss of several forebrain markers. However, the remaining tissues reconstituted Gsc and Shh activity and expressed the ventral forebrain marker Nkx2.1. Furthermore, analysis of Gsc-deficient embryos reveals that the morphogenetic function of the rostral AML requires Gsc activity. Removal of the caudal AML led to a complete loss of midline molecular markers anterior to the 4th somite. In addition, Nkx2.1 expression was not detected in the ventral neural tube. The maintenance and function of the rostral AML therefore require inductive signals emanating from the caudal AML. Our results point to a role for AML in the refinement of the anteroposterior patterning and morphogenesis of the brain.

Sign in / Sign up

Export Citation Format

Share Document