scholarly journals Proteins and Mechanisms Regulating Gap-Junction Assembly, Internalization, and Degradation

Physiology ◽  
2013 ◽  
Vol 28 (2) ◽  
pp. 93-116 ◽  
Author(s):  
Anastasia F. Thévenin ◽  
Tia J. Kowal ◽  
John T. Fong ◽  
Rachael M. Kells ◽  
Charles G. Fisher ◽  
...  

Gap junctions (GJs) are the only known cellular structures that allow a direct cell-to-cell transfer of signaling molecules by forming densely packed arrays or “plaques” of hydrophilic channels that bridge the apposing membranes of neighboring cells. The crucial role of GJ-mediated intercellular communication (GJIC) for all aspects of multicellular life, including coordination of development, tissue function, and cell homeostasis, has been well documented. Assembly and degradation of these membrane channels is a complex process that includes biosynthesis of the connexin (Cx) subunit proteins (innexins in invertebrates) on endoplasmic reticulum (ER) membranes, oligomerization of compatible subunits into hexameric hemichannels (connexons), delivery of the connexons to the plasma membrane (PM), head-on docking of compatible connexons in the extracellular space at distinct locations, arrangement of channels into dynamic spatially and temporally organized GJ channel plaques, as well as internalization of GJs into the cytoplasm followed by their degradation. Clearly, precise modulation of GJIC, biosynthesis, and degradation are crucial for accurate function, and much research currently addresses how these fundamental processes are regulated. Here, we review posttranslational protein modifications (e.g., phosphorylation and ubiquitination) and the binding of protein partners (e.g., the scaffolding protein ZO-1) known to regulate GJ biosynthesis, internalization, and degradation. We also look closely at the atomic resolution structure of a GJ channel, since the structure harbors vital cues relevant to GJ biosynthesis and turnover.

1970 ◽  
Vol 7 (1) ◽  
pp. 75-79 ◽  
Author(s):  
F. W. Gay ◽  
J. K. Clarke ◽  
E. Dermott

2014 ◽  
Vol 164 (5) ◽  
pp. 359-365 ◽  
Author(s):  
Venugopal Thayanithy ◽  
Elizabeth L. Dickson ◽  
Clifford Steer ◽  
Subbaya Subramanian ◽  
Emil Lou

2004 ◽  
Vol 199 (2) ◽  
pp. 283-293 ◽  
Author(s):  
Clare Jolly ◽  
Kirk Kashefi ◽  
Michael Hollinshead ◽  
Quentin J. Sattentau

Direct cell–cell transfer is an efficient mechanism of viral dissemination within an infected host, and human immunodeficiency virus 1 (HIV-1) can exploit this mode of spread. Receptor recognition by HIV-1 occurs via interactions between the viral surface envelope glycoprotein (Env), gp120, and CD4 and a chemokine receptor, CCR5 or CXCR4. Here, we demonstrate that the binding of CXCR4-using HIV-1–infected effector T cells to primary CD4+/CXCR4+ target T cells results in rapid recruitment to the interface of CD4, CXCR4, talin, and lymphocyte function–associated antigen 1 on the target cell, and of Env and Gag on the effector cell. Recruitment of these membrane molecules into polarized clusters was dependent on Env engagement of CD4 and CXCR4 and required remodelling of the actin cytoskeleton. Transfer of Gag from effector to target cell was observed by 1 h after conjugate formation, was independent of cell–cell fusion, and was probably mediated by directed virion fusion with the target cell. We propose that receptor engagement by Env directs the rapid, actin-dependent recruitment of HIV receptors and adhesion molecules to the interface, resulting in a stable adhesive junction across which HIV infects the target cell.


Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 483
Author(s):  
Supasek Kongsomros ◽  
Suwimon Manopwisedjaroen ◽  
Jarinya Chaopreecha ◽  
Sheng-Fan Wang ◽  
Suparerk Borwornpinyo ◽  
...  

Viruses have developed direct cell-to-cell transfer strategies to enter target cells without being released to escape host immune responses and antiviral treatments. These strategies are more rapid and efficient than transmission through indirect mechanisms of viral infection between cells. Here, we demonstrate that an H5N1 influenza virus can spread via direct cell-to-cell transfer in Madin-Darby canine kidney (MDCK) cells. We compared cell-to-cell transmission of the H5N1 virus to that of a human influenza H1N1 virus. The H5N1 virus has been found to spread to recipient cells faster than the human influenza H1N1 virus. Additionally, we showed that plasma membrane exchange (trogocytosis) occurs between co-cultured infected donor cells and uninfected recipient cells early point, allowing the intercellular transfer of viral material to recipient cells. Notably, the H5N1 virus induced higher trogocytosis levels than the H1N1 virus, which could explain the faster cell-to-cell transmission rate of H5N1. Importantly, this phenomenon was also observed in A549 human lung epithelial cells, which are representative cells in the natural infection site. Altogether, our results provide evidence demonstrating that trogocytosis could be the additional mechanism utilized by the H5N1 virus for rapid and efficient cell-to-cell transmission.


Author(s):  
Walter Pohl

When the Gothic War began in Italy in 535, the country still conserved many features of classical culture and late antique administration. Much of that was lost in the political upheavals of the following decades. Building on Chris Wickham’s work, this contribution sketches an integrated perspective of these changes, attempting to relate the contingency of events to the logic of long-term change, discussing political options in relation to military and economic means, and asking in what ways the erosion of consensus may be understood in a cultural and religious context. What was the role of military entrepreneurs of more or less barbarian or Roman extraction in the distribution or destruction of resources? How did Christianity contribute to the transformation of ancient society? The old model of barbarian invasions can contribute little to understanding this complex process. It is remarkable that for two generations, all political strategies in Italy ultimately failed.


Cell Reports ◽  
2021 ◽  
Vol 35 (10) ◽  
pp. 109189
Author(s):  
Eleanna Kara ◽  
Alessandro Crimi ◽  
Anne Wiedmer ◽  
Marc Emmenegger ◽  
Claudia Manzoni ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nathanael A. Caveney ◽  
Sean D. Workman ◽  
Rui Yan ◽  
Claire E. Atkinson ◽  
Zhiheng Yu ◽  
...  

AbstractThe pathway for the biosynthesis of the bacterial cell wall is one of the most prolific antibiotic targets, exemplified by the widespread use of β-lactam antibiotics. Despite this, our structural understanding of class A penicillin binding proteins, which perform the last two steps in this pathway, is incomplete due to the inherent difficulty in their crystallization and the complexity of their substrates. Here, we determine the near atomic resolution structure of the 83 kDa class A PBP from Escherichia coli, PBP1b, using cryogenic electron microscopy and a styrene maleic acid anhydride membrane mimetic. PBP1b, in its apo form, is seen to exhibit a distinct conformation in comparison to Moenomycin-bound crystal structures. The work herein paves the way for the use of cryoEM in structure-guided antibiotic development for this notoriously difficult to crystalize class of proteins and their complex substrates.


Author(s):  
Hans Liljenström

AbstractWhat is the role of consciousness in volition and decision-making? Are our actions fully determined by brain activity preceding our decisions to act, or can consciousness instead affect the brain activity leading to action? This has been much debated in philosophy, but also in science since the famous experiments by Libet in the 1980s, where the current most common interpretation is that conscious free will is an illusion. It seems that the brain knows, up to several seconds in advance what “you” decide to do. These studies have, however, been criticized, and alternative interpretations of the experiments can be given, some of which are discussed in this paper. In an attempt to elucidate the processes involved in decision-making (DM), as an essential part of volition, we have developed a computational model of relevant brain structures and their neurodynamics. While DM is a complex process, we have particularly focused on the amygdala and orbitofrontal cortex (OFC) for its emotional, and the lateral prefrontal cortex (LPFC) for its cognitive aspects. In this paper, we present a stochastic population model representing the neural information processing of DM. Simulation results seem to confirm the notion that if decisions have to be made fast, emotional processes and aspects dominate, while rational processes are more time consuming and may result in a delayed decision. Finally, some limitations of current science and computational modeling will be discussed, hinting at a future development of science, where consciousness and free will may add to chance and necessity as explanation for what happens in the world.


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