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Mechanobiology of Bladder Urothelial Cells
Published in Jiro Nagatomi, Eno Essien Ebong, Mechanobiology Handbook, 2018
Shawn Olsen, Kevin Champaigne, Jiro Nagatomi
Another potential mechanism for mechanically induced ATP release involves the transport of the molecule through connexin or pannexin hemichannels [34,35]. Connexins are transmembrane proteins that form gap junctions with adjacent cells and allow the passage of ions and small molecules of less than approximately 1 kDa directly between the cytoplasmic volumes of connected cells [27]. In addition to the traditional paired channels of a gap junction, the existence of nonjunctional connexin hemichannels on the surface of cells has been observed, where no corresponding channel on a neighboring cell is present [36]. Although normally closed, under certain circumstances including a low extracellular calcium concentration, these channels can open to provide a route for solutes including ATP to pass between the cytoplasm and the extracellular space [37]. Connexin hemichannels may thereby participate in intercellular signaling processes by providing similar functionality to traditional ion channels, but for larger molecules such as ATP.
Cell–Cell Communications through Gap Junctions and Cancer in 3D Systems
Published in Karen J.L. Burg, Didier Dréau, Timothy Burg, Engineering 3D Tissue Test Systems, 2017
Stephanie Nicole Shishido, Thu Annelise Nguyen
Gap junctions are protein channels made of the protein connexin (Cx). Connexins have four hydrophobic membrane spanning domains: two conserved, extracellular domains involved in paired hemichannel docking and three cytoplasmic domains (Figure 13.1) (Saez et al. 2003). Intercellular channels are formed through oligomerization of six connexins into a hexameric hemichannel called a connexon, which is trafficked to the plasma membrane. Hemichannels allow communication between cytoplasm and extracellular space. On the membrane, the connexon floats laterally until it docks with a second connexon on the adjacent cell to form an intact gap junction channel. Groups of these channels form gap junctional plaques, allowing the flow of small molecules between the cytosol of neighboring cells.
Synapses
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
Finally, the following properties of electrical synapses should be noted: In contrast to chemical synapses, there is no amplification at electrical synapses. In fact, the presynaptic cell sees what is essentially the resistance of the channel in series with the parallel resistance and capacitance on the postsynaptic side (Problem 6.5). This causes some attenuation as well as slowing of the voltage response because of the time it takes to charge the membrane capacitor on the postsynaptic side. In other words, the voltage response is low-pass. The attenuation and delay are smaller, the larger the presynaptic cell is compared to the postsynaptic cell, and the more numerous are the gap junctions connecting the two cells. The delay is typically a fraction of a millisecond but can be comparable in some cases to that at the fastest chemical synapses.Because of the electrical coupling between the presynaptic and postsynaptic cells, the size and shape of the voltage signal at the postsynaptic cell are directly related to the size and shape of the voltage signal at the presynaptic cell.A current flowing between a more depolarized cell A to a less depolarized cell B tends to excite cell B and inhibit cell A because of the reduced depolarization in cell A due to charge movement to cell B. This is discussed in Section 7.2.4.1.Repetitive stimulation of electrical synapses does not lead to facilitation or depression as in chemical synapses.The gap junctions allow chemical continuity for small molecules. The chemical continuity appears to be particularly important during development, as many gap junctions between cells disappear after maturation.Mutations in connexin genes can cause a variety of diseases, including peripheral neuropathy associated with abnormal Schwann cells that lack normal connexins.
Targeting gap junctional intercellular communication by hepatocarcinogenic compounds
Published in Journal of Toxicology and Environmental Health, Part B, 2020
Kaat Leroy, Alanah Pieters, Andrés Tabernilla, Axelle Cooreman, Raf Van Campenhout, Bruno Cogliati, Mathieu Vinken
Gap junctions are a group of cell-to-cell contacts composed of 2 hemichannels of adjacent cells, which in turn are built up by 6 connexin (Cx) proteins (Figure 1) (Cooreman et al. 2019). Thus far, more than 21 human connexin family members were identified, all that are expressed in a cell type-specific manner (Cooreman et al. 2019; Tachikawa et al. 2020). In liver, hepatocytes abundantly produce Cx32 and to a lesser extent Cx26, whereas non-parenchymal hepatic cell populations, including Kupffer cells, endothelial cells and stellate cells, mainly express Cx43 (Berthoud et al. 1992; Fischer et al. 2005; Greenwel et al. 1993; Saez 1997). Cx32 is uniformly produced by hepatocytes, while Cx26 is preferentially expressed in the periportal acinar area (Rosenberg, Spray, and Reid 1992). All connexin proteins are named after their respective molecular weight and share the same topology consisting of 4 transmembrane regions, 2 extracellular loops, 1 cytoplasmic loop and an intracellular C-terminus and N-terminus. Approximately 3% of the membrane surface of hepatocytes is covered with gap junctions, which are organized in plaques. A gap junction typically measures 180Å in length and 15Å in diameter, enabling passive diffusion of small and hydrophilic molecules, such as glutamate, glucose, inositol trisphosphate, glutathione, adenosine trisphosphate and cyclic adenosine monophosphate (cAMP), as well as ions, including calcium, potassium and sodium (Vinken et al. 2008b). Thus, gap junctions control all facets of the cellular life cycle ranging from cell growth to cell death (Vinken et al. 2006).
The impact of radicals in cold atmospheric plasma on the structural modification of gap junction: a reactive molecular dynamics study
Published in International Journal of Smart and Nano Materials, 2019
Rong-Guang Xu, Zhitong Chen, Michael Keidar, Yongsheng Leng
Gap junctions are specialized intercellular communication channels between neighboring cells with an apparent separation gap of 2–4 nm, which permit the exchange of various ions and small molecules through a regulated gate. A schematic picture of gap junction and connexins are shown in Figure 1. Each gap junction is composed of two apposed hemichannels termed as connexons contributed by each cell. Individual connexon is made up of six protein subunits called connexins (Cx) monomers formed from a family of 21 human proteins. The structure of connexin 26 (Cx26 – a typical connexin in humans) with molecular configuration can be obtained from protein data bank (accession no. 2Zw3) as shown in Figure 2. Connexin is a transmembrane protein with four transmembrane domains (TM1 to TM4). They are connected by two extracellular loops (EL-1 and EL-2) and one cytoplasmic loop (CL). Each connexin contains amino (NT) and carboxyl (CT) terminus in the cytoplasm.
Liver tumor potency indicators for technical toxaphene and congeners simulating weathered toxaphene
Published in Human and Ecological Risk Assessment: An International Journal, 2018
Brent D. Kerger, Kenneth T. Bogen, Anne E. Loccisano, James C. Lamb
GJIC inhibition is thought to occur as the result of altered gene expression and/or perturbation of cellular metabolism of connexins, a family of proteins that form channels between mammalian cells that allow ions and small molecules to be transferred between cells thereby fostering metabolic cooperation and homeostasis across tissues (Aasen et al.2016; Falk et al.2016; Kjenseth et al.2010; Sirnes et al.2009). Connexins act as building blocks for the gap junctions and associated cellular structures, but also appear to serve as tumor suppressors, such that the outcome of GJIC inhibition may reflect nullified tumor suppression and/or reduced connexin expression or functionality (Aasen et al.2016; Falk et al.2016). Dysregulated ubiquitination or protein kinase activities, e.g., protein kinase C, mitogen-associate protein kinase (MAPK), and extracellular signal-regulated kinases (ERK), can affect degradation of connexins and cause GJIC inhibition, a process that likely involves cross-talk between multiple cellular receptors like epidermal growth factor receptors, MAPK/ERK pathway receptors, and others (Rivedal and Opsahl 2001; Sirnes et al.2009; Kjenseth et al.2010; Falk et al.2016). Although CAR activation has not been directly linked to GJIC inhibition, many CAR agonists like toxaphene that promote hyperplastic and neoplastic liver cell growth, such phenobabital and clofibrate, upregulate expression of numerous receptor-mediated metabolic and epigenetic pathways; this may include the Wnt/beta-catenin pathway that involves cross-talk with CAR and (via beta-catenin) is also linked to GJIC inhibition (Li et al.2015, 2017; Kazantseva et al.2016).