scholarly journals Neuronal SUMOylation: Mechanisms, Physiology, and Roles in Neuronal Dysfunction

2014 ◽  
Vol 94 (4) ◽  
pp. 1249-1285 ◽  
Author(s):  
Jeremy M. Henley ◽  
Tim J. Craig ◽  
Kevin A. Wilkinson
Keyword(s):  
Protein Trafficking ◽  
Protein Modification ◽  
Synapse Formation ◽  
Neuronal Dysfunction ◽  
Cellular Physiology ◽  
Cellular Processes ◽  
Posttranslational Protein Modification ◽  
And Function ◽  
And Control ◽  
Protein Sumoylation

Protein SUMOylation is a critically important posttranslational protein modification that participates in nearly all aspects of cellular physiology. In the nearly 20 years since its discovery, SUMOylation has emerged as a major regulator of nuclear function, and more recently, it has become clear that SUMOylation has key roles in the regulation of protein trafficking and function outside of the nucleus. In neurons, SUMOylation participates in cellular processes ranging from neuronal differentiation and control of synapse formation to regulation of synaptic transmission and cell survival. It is a highly dynamic and usually transient modification that enhances or hinders interactions between proteins, and its consequences are extremely diverse. Hundreds of different proteins are SUMO substrates, and dysfunction of protein SUMOylation is implicated in a many different diseases. Here we briefly outline core aspects of the SUMO system and provide a detailed overview of the current understanding of the roles of SUMOylation in healthy and diseased neurons.

scholarly journals Who's really in control: microbial regulation of protein trafficking in the epithelium

2014 ◽  
Vol 306 (3) ◽  
pp. C187-C197 ◽  
Author(s):  
Matthew R. Hendricks ◽  
Jennifer M. Bomberger
Keyword(s):  
Epithelial Cell ◽  
Protein Trafficking ◽  
Host Cells ◽  
Eukaryotic Cells ◽  
Cell Physiology ◽  
Cellular Physiology ◽  
Cellular Processes ◽  
Complex Interactions ◽  
Host Pathogen ◽  
Host Tissues

Due to evolutionary pressure, there are many complex interactions at the interface between pathogens and eukaryotic host cells wherein host cells attempt to clear invading microorganisms and pathogens counter these mechanisms to colonize and invade host tissues. One striking observation from studies focused on this interface is that pathogens have multiple mechanisms to modulate and disrupt normal cellular physiology to establish replication niches and avoid clearance. The precision by which pathogens exert their effects on host cells makes them excellent tools to answer questions about cell physiology of eukaryotic cells. Furthermore, an understanding of these mechanisms at the host-pathogen interface will benefit our understanding of how pathogens cause disease. In this review, we describe a few examples of how pathogens disrupt normal cellular physiology and protein trafficking at epithelial cell barriers to underscore how pathogens modulate cellular processes to cause disease and how this knowledge has been utilized to learn about cellular physiology.

scholarly journals Hypoxia. 4. Hypoxia and ion channel function

2011 ◽  
Vol 300 (5) ◽  
pp. C951-C967 ◽  
Author(s):  
Larissa A. Shimoda ◽  
Jan Polak
Keyword(s):  
Ion Channels ◽  
Cell Function ◽  
Critical Role ◽  
Cardiac Contractility ◽  
Cell Types ◽  
Cellular Processes ◽  
Oxygen Sensitive ◽  
Sense And Respond ◽  
And Function ◽  
And Control

The ability to sense and respond to oxygen deprivation is required for survival; thus, understanding the mechanisms by which changes in oxygen are linked to cell viability and function is of great importance. Ion channels play a critical role in regulating cell function in a wide variety of biological processes, including neuronal transmission, control of ventilation, cardiac contractility, and control of vasomotor tone. Since the 1988 discovery of oxygen-sensitive potassium channels in chemoreceptors, the effect of hypoxia on an assortment of ion channels has been studied in an array of cell types. In this review, we describe the effects of both acute and sustained hypoxia (continuous and intermittent) on mammalian ion channels in several tissues, the mode of action, and their contribution to diverse cellular processes.

scholarly journals Knockout of the Golgi stacking proteins GRASP55 and GRASP65 impairs Golgi structure and function

2017 ◽  
Vol 28 (21) ◽  
pp. 2833-2842 ◽  
Author(s):  
Michael E. Bekier ◽  
Leibin Wang ◽  
Jie Li ◽  
Haoran Huang ◽  
Danming Tang ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Protein Trafficking ◽  
Critical Role ◽  
Hek293 Cells ◽  
Double Knockout ◽  
Knock Out ◽  
Golgi Stack ◽  
Cellular Processes ◽  
Golgi Structure ◽  
And Function

Golgi reassembly stacking protein of 65 kDa (GRASP65) and Golgi reassembly stacking protein of 55 kDa (GRASP55) were originally identified as Golgi stacking proteins; however, subsequent GRASP knockdown experiments yielded inconsistent results with respect to the Golgi structure, indicating a limitation of RNAi-based depletion. In this study, we have applied the recently developed clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology to knock out GRASP55 and GRASP65, individually or in combination, in HeLa and HEK293 cells. We show that double knockout of GRASP proteins disperses the Golgi stack into single cisternae and tubulovesicular structures, accelerates protein trafficking, and impairs accurate glycosylation of proteins and lipids. These results demonstrate a critical role for GRASPs in maintaining the stacked structure of the Golgi, which is required for accurate posttranslational modifications in the Golgi. Additionally, the GRASP knockout cell lines developed in this study will be useful tools for studying the role of GRASP proteins in other important cellular processes.

scholarly journals No Longer Underappreciated: The Emerging Concept of Astrocyte Heterogeneity in Neuroscience

2020 ◽  
Vol 10 (3) ◽  
pp. 168 ◽  
Author(s):  
Francisco Pestana ◽  
Gabriela Edwards-Faret ◽  
T. Grant Belgard ◽  
Araks Martirosyan ◽  
Matthew G. Holt
Keyword(s):  
Brain Function ◽  
Synapse Formation ◽  
Normal Brain ◽  
Barrier Formation ◽  
Astrocyte Heterogeneity ◽  
Normal Brain Function ◽  
The Central Nervous System ◽  
And Function ◽  
And Control

Astrocytes are ubiquitous in the central nervous system (CNS). These cells possess thousands of individual processes, which extend out into the neuropil, interacting with neurons, other glia and blood vessels. Paralleling the wide diversity of their interactions, astrocytes have been reported to play key roles in supporting CNS structure, metabolism, blood-brain-barrier formation and control of vascular blood flow, axon guidance, synapse formation and modulation of synaptic transmission. Traditionally, astrocytes have been studied as a homogenous group of cells. However, recent studies have uncovered a surprising degree of heterogeneity in their development and function, in both the healthy and diseased brain. A better understanding of astrocyte heterogeneity is urgently needed to understand normal brain function, as well as the role of astrocytes in response to injury and disease.

scholarly journals FADD in Cancer: Mechanisms of Altered Expression and Function, and Clinical Implications

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1462 ◽  
Author(s):  
José L Marín-Rubio ◽  
Laura Vela-Martín ◽  
José Fernández-Piqueras ◽  
María Villa-Morales
Keyword(s):  
Posttranslational Modifications ◽  
Cell Cycle Control ◽  
Regulation Of Gene Expression ◽  
Death Receptor ◽  
Clinical Implications ◽  
Altered Expression ◽  
Cellular Processes ◽  
Potential Biomarker ◽  
And Function ◽  
And Control

FADD was initially described as an adaptor molecule for death receptor-mediated apoptosis, but subsequently it has been implicated in nonapoptotic cellular processes such as proliferation and cell cycle control. During the last decade, FADD has been shown to play a pivotal role in most of the signalosome complexes, such as the necroptosome and the inflammasome. Interestingly, various mechanisms involved in regulating FADD functions have been identified, essentially posttranslational modifications and secretion. All these aspects have been thoroughly addressed in previous reviews. However, FADD implication in cancer is complex, due to pleiotropic effects. It has been reported either as anti- or protumorigenic, depending on the cell type. Regulation of FADD expression in cancer is a complex issue since both overexpression and downregulation have been reported, but the mechanisms underlying such alterations have not been fully unveiled. Posttranslational modifications also constitute a relevant mechanism controlling FADD levels and functions in tumor cells. In this review, we aim to provide detailed, updated information on alterations leading to changes in FADD expression and function in cancer. The participation of FADD in various biological processes is recapitulated, with a mention of interesting novel functions recently proposed for FADD, such as regulation of gene expression and control of metabolic pathways. Finally, we gather all the available evidence regarding the clinical implications of FADD alterations in cancer, especially as it has been proposed as a potential biomarker with prognostic value.

Ca2+-Activated K+ Channels: From Protein Complexes to Function

2010 ◽  
Vol 90 (4) ◽  
pp. 1437-1459 ◽  
Author(s):  
Henrike Berkefeld ◽  
Bernd Fakler ◽  
Uwe Schulte
Keyword(s):  
Protein Interactions ◽  
Muscle Tone ◽  
Protein Complexes ◽  
Neuronal Firing ◽  
Protein Protein Interactions ◽  
Cellular Processes ◽  
And Function ◽  
And Control ◽  
Proteomic Research ◽  
Partner Proteins

Molecular research on ion channels has demonstrated that many of these integral membrane proteins associate with partner proteins, often versatile in their function, or even assemble into stable macromolecular complexes that ensure specificity and proper rate of the channel-mediated signal transduction. Calcium-activated potassium (KCa) channels that link excitability and intracellular calcium concentration are responsible for a wide variety of cellular processes ranging from regulation of smooth muscle tone to modulation of neurotransmission and control of neuronal firing pattern. Most of these functions are brought about by interaction of the channels' pore-forming subunits with distinct partner proteins. In this review we summarize recent insights into protein complexes associated with KCa channels as revealed by proteomic research and discuss the results available on structure and function of these complexes and on the underlying protein-protein interactions. Finally, the results are related to their significance for the function of KCa channels under cellular conditions.

scholarly journals Characterization of the Ubiquitin-Modified Proteome Regulated by Transient Forebrain Ischemia

2013 ◽  
Vol 34 (3) ◽  
pp. 425-432 ◽  
Author(s):  
Masahiro Iwabuchi ◽  
Huaxin Sheng ◽  
JWill Thompson ◽  
Liangli Wang ◽  
Laura G Dubois ◽  
...  
Keyword(s):  
Protein Modification ◽  
Internal Standard ◽  
Forebrain Ischemia ◽  
Label Free ◽  
Cellular Processes ◽  
Damage Repair ◽  
Liquid Chromatography Tandem Mass ◽  
Posttranslational Protein Modification ◽  
Neuronal Functions

Ubiquitylation is a posttranslational protein modification that modulates various cellular processes of key significance, including protein degradation and DNA damage repair. In animals subjected to transient cerebral ischemia, ubiquitin-conjugated proteins accumulate in Triton-insoluble aggregates. Although this process is widely considered to modulate the fate of postischemic neurons, few attempts have been made to characterize the ubiquitin-modified proteome in these aggregates. We performed proteomics analyses to identify ubiquitylated proteins in postischemic aggregates. Mice were subjected to 10 minutes of forebrain ischemia and 4 hours of reperfusion. The hippocampi were dissected, aggregates were isolated, and trypsin-digested after spiking with GG-BSA as internal standard. K- ε-GG-containing peptides were immunoprecipitated and analyzed by label-free quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. We identified 1,664 peptides to 520 proteins containing at least one K- ε-GG. Sixty-six proteins were highly ubiquitylated, with 10 or more K- ε-GG peptides. Based on selection criteria of greater than fivefold increase and P<0.001, 763 peptides to 272 proteins were highly enriched in postischemic aggregates. These included proteins involved in important neuronal functions and signaling pathways that are impaired after ischemia. Results of this study could serve as an important platform to uncover the mechanisms linking insoluble ubiquitin aggregates to the functions of postischemic neurons.

scholarly journals Bend, Push, Stretch: Remarkable Structure and Mechanics of Single Intermediate Filaments and Meshworks

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1960
Author(s):  
K. Tanuj Sapra ◽  
Ohad Medalia
Keyword(s):  
Intermediate Filaments ◽  
Eukaryotic Cell ◽  
Coiled Coils ◽  
Cellular Functions ◽  
Mechanical Pressure ◽  
Mechanical Feature ◽  
Cellular Processes ◽  
Nuclear Lamins ◽  
Filament Networks ◽  
And Function

The cytoskeleton of the eukaryotic cell provides a structural and functional scaffold enabling biochemical and cellular functions. While actin and microtubules form the main framework of the cell, intermediate filament networks provide unique mechanical properties that increase the resilience of both the cytoplasm and the nucleus, thereby maintaining cellular function while under mechanical pressure. Intermediate filaments (IFs) are imperative to a plethora of regulatory and signaling functions in mechanotransduction. Mutations in all types of IF proteins are known to affect the architectural integrity and function of cellular processes, leading to debilitating diseases. The basic building block of all IFs are elongated α-helical coiled-coils that assemble hierarchically into complex meshworks. A remarkable mechanical feature of IFs is the capability of coiled-coils to metamorphize into β-sheets under stress, making them one of the strongest and most resilient mechanical entities in nature. Here, we discuss structural and mechanical aspects of IFs with a focus on nuclear lamins and vimentin.

scholarly journals Metagenomic Analysis of the Fecal Archaeome in Suckling Piglets Following Perinatal Tulathromycin Metaphylaxis

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1825
Author(s):  
Mohamed Zeineldin ◽  
Ameer Megahed ◽  
Benjamin Blair ◽  
Brian Aldridge ◽  
James Lowe
Keyword(s):  
Sequencing Analysis ◽  
Metagenomic Sequencing ◽  
Post Intervention ◽  
Gastrointestinal Microbiome ◽  
Health And Wellbeing ◽  
Suckling Piglets ◽  
And Function ◽  
Changes Over Time ◽  
And Control ◽  
The Impact

The gastrointestinal microbiome plays an important role in swine health and wellbeing, but the gut archaeome structure and function in swine remain largely unexplored. To date, no metagenomics-based analysis has been done to assess the impact of an early life antimicrobials intervention on the gut archaeome. The aim of this study was to investigate the effects of perinatal tulathromycin (TUL) administration on the fecal archaeome composition and diversity in suckling piglets using metagenomic sequencing analysis. Sixteen litters were administered one of two treatments (TUL; 2.5 mg/kg IM and control (CONT); saline 1cc IM) soon after birth. Deep fecal swabs were collected from all piglets on days 0 (prior to treatment), 5, and 20 post intervention. Each piglet’s fecal archaeome was composed of rich and diverse communities that showed significant changes over time during the suckling period. At the phylum level, 98.24% of the fecal archaeome across all samples belonged to Euryarchaeota. At the genus level, the predominant archaeal genera across all samples were Methanobrevibacter (43.31%), Methanosarcina (10.84%), Methanococcus (6.51%), and Methanocorpusculum (6.01%). The composition and diversity of the fecal archaeome between the TUL and CONT groups at the same time points were statistically insignificant. Our findings indicate that perinatal TUL metaphylaxis seems to have a minimal effect on the gut archaeome composition and diversity in sucking piglets. This study improves our current understanding of the fecal archaeome structure in sucking piglets and provides a rationale for future studies to decipher its role in and impact on host robustness during this critical phase of production.

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