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https://www.readbyqxmd.com/read/29760196/perinodal-adipose-tissue-participates-in-immune-protection-through-a-lymphatic-vessel-independent-route
#1
Yujia Lin, Glory Leung, Dante Louie, Ania Bogoslowski, James Ross, Paul Kubes, Pierre-Yves von der Weid, Shan Liao
Lymphatic vessels remove and transport excess interstitial fluid to lymph nodes (LNs) for fluid balance and immune protection. LNs are typically surrounded by perinodal adipose tissue (PAT). However, PAT is a blood vessel-rich but lymphatic-rare tissue; therefore, how excess fluid in PAT is removed remains unclear. Using C57BL/6 mice, fluorescent dye tracing and transmission electron microscopy results suggest that fluid in PAT can travel to the LN via collagen I+ channels (PAT-LN conduits), merge into a collagen-rich space between the PAT and LN capsule (PAT-LN sinus), and may enter the LN via the LN capsule-associated conduits...
May 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29750923/ion-channel-modulators-in-cystic-fibrosis
#2
REVIEW
Martina Gentzsch, Marcus A Mall
Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and remains one of the most common life-shortening genetic diseases affecting the lung and other organs. CFTR functions as a cAMP-dependent anion channel that transports chloride and bicarbonate across epithelial surfaces and disruption of these ion transport processes plays a central role in the pathogenesis of CF. These findings provided the rationale for pharmacological modulation of ion transport, either by targeting mutant CFTR or alternative ion channels that can compensate for CFTR dysfunction, as a promising therapeutic approach...
May 8, 2018: Chest
https://www.readbyqxmd.com/read/29749636/axon-initial-segments-structure-function-and-disease
#3
REVIEW
Claire Yu-Mei Huang, Matthew N Rasband
The axon initial segment (AIS) is located at the proximal axon and is the site of action potential initiation. This reflects the high density of ion channels found at the AIS. Adaptive changes to the location and length of the AIS can fine-tune the excitability of neurons and modulate plasticity in response to activity. The AIS plays an important role in maintaining neuronal polarity by regulating the trafficking and distribution of proteins that function in somatodendritic or axonal compartments of the neuron...
May 11, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29748711/calcium-and-voltage-gated-bk-channels-in-vascular-smooth-muscle
#4
REVIEW
Alex M Dopico, Anna N Bukiya, Jonathan H Jaggar
Ion channels in vascular smooth muscle regulate myogenic tone and vessel contractility. In particular, activation of calcium- and voltage-gated potassium channels of large conductance (BK channels) results in outward current that shifts the membrane potential toward more negative values, triggering a negative feed-back loop on depolarization-induced calcium influx and SM contraction. In this short review, we first present the molecular basis of vascular smooth muscle BK channels and the role of subunit composition and trafficking in the regulation of myogenic tone and vascular contractility...
May 11, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29748463/protein%C3%A2-protein-interactions-with-connexin-43-regulation-and-function
#5
REVIEW
Paul L Sorgen, Andrew J Trease, Gaelle Spagnol, Mario Delmar, Morten S Nielsen
Connexins are integral membrane building blocks that form gap junctions, enabling direct cytoplasmic exchange of ions and low-molecular-mass metabolites between adjacent cells. In the heart, gap junctions mediate the propagation of cardiac action potentials and the maintenance of a regular beating rhythm. A number of connexin interacting proteins have been described and are known gap junction regulators either through direct effects (e.g., kinases) or the formation of larger multifunctional complexes (e.g., cytoskeleton scaffold proteins)...
May 10, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29739907/clag3-self-associates-in-malaria-parasites-and-quantitatively-determines-nutrient-uptake-channels-at-the-host-membrane
#6
Ankit Gupta, Praveen Balabaskaran-Nina, Wang Nguitragool, Gagandeep S Saggu, Marc A Schureck, Sanjay A Desai
Malaria parasites increase host erythrocyte permeability to ions and nutrients via a broad-selectivity channel known as the plasmodial surface anion channel (PSAC), linked to parasite-encoded CLAG3 and two associated proteins. These proteins lack the multiple transmembrane domains typically present in channel-forming proteins, raising doubts about their precise roles. Using the virulent human Plasmodium falciparum parasite, we report that CLAG3 undergoes self-association and that this protein's expression determines channel phenotype quantitatively...
May 8, 2018: MBio
https://www.readbyqxmd.com/read/29737520/na-restriction-activates-enac-in-rat-kidney-through-two-mechanisms-and-decreases-distal-na-delivery
#7
Gustavo Frindt, Lei Yang, Krister Bamberg, Lawrence G Palmer
KEY POINTS: Dietary Na restriction, through the mineralocorticoid aldosterone, acts on epithelial Na channels (ENaC) through both fast (24 hrs) and slow (5 to 7 days) mechanisms in the kidney. The fast effect entails increased proteolytic processing and trafficking of channel protein to the apical membrane. It is rapidly reversible by the mineralocorticoid receptor antagonist eplerenone and is largely lost when tubules are studied ex vivo. The slow effect does not require increased processing or surface expression, is refractory to acute eplerenone treatment, and is preserved ex vivo...
May 8, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29735519/-salmonella-tol-pal-reduces-outer-membrane-glycerophopholipid-levels-for-envelope-homeostasis-and-survival-during-bacteremia
#8
Revathi Masilamani, Melina B Cian, Zachary D Dalebroux
Salmonellae regulate membrane lipids during infection, but the exact proteins and mechanisms that promote their survival during bacteremia remain largely unknown. Mutations in genes encoding the conserved Salmonella enterica serovar Typhimurium (STm) Tol-Pal apparatus caused the outer-membrane (OM)-sensor lipoprotein, RcsF, to become activated. The capsule activation phenotype for the mutants suggested that Tol-Pal might influence envelope-lipid homeostasis. The mechanism involves reducing OM-glycerophospholipid (GPL) levels, since the mutant salmonellae similarly accumulated phosphatidylglycerols (PGl) and phosphatidylethanolamines (PE) compared to the wild type...
May 7, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29726084/increased-ca-uptake-by-erythrocytes-infected-with-malaria-parasites-evidence-for-exported-proteins-and-novel-inhibitors
#9
Ambuj K Kushwaha, Liana Apolis, Daisuke Ito, Sanjay A Desai
Malaria parasites export many proteins into their host erythrocytes and increase membrane permeability to diverse solutes. While most solutes use a broad-selectivity channel known as the plasmodial surface anion channel (PSAC), increased Ca++ uptake is mediated by a distinct, poorly characterized mechanism that appears to be essential for the intracellular parasite. Here, we examined infected cell Ca++ uptake with a kinetic fluorescence assay and the virulent human pathogen, P. falciparum. Cell surface labeling with N-hydroxysulfosuccinimide esters revealed differing effects on transport into infected and uninfected cells, indicating that Ca++ uptake at the infected cell surface is mediated by new or altered proteins at the host membrane...
May 3, 2018: Cellular Microbiology
https://www.readbyqxmd.com/read/29725305/development-of-a-high-throughput-flow-cytometry-assay-to-monitor-defective-trafficking-and-rescue-of-long-qt2-mutant-herg-channels
#10
Scott A Kanner, Ananya Jain, Henry M Colecraft
Long QT Syndrome (LQTS) is an acquired or inherited disorder characterized by prolonged QT interval, exertion-triggered arrhythmias, and sudden cardiac death. One of the most prevalent hereditary LQTS subtypes, LQT2, results from loss-of-function mutations in the hERG channel, which conducts I Kr , the rapid component of the delayed rectifier K+ current, critical for cardiac repolarization. The majority of LQT2 mutations result in Class 2 deficits characterized by impaired maturation and trafficking of hERG channels...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29724910/retromer-associates-with-the-cytoplasmic-amino-terminus-of-polycystin-2
#11
Frances C Tilley, Matthew Gallon, Chong Luo, Chris M Danson, Jing Zhou, Peter J Cullen
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic human disease, with around 12.5 million people affected worldwide. ADPKD results from mutations in either PKD1 or PKD2 , which encode the atypical G-protein coupled receptor polycystin-1 (PC1) and the transient receptor potential channel polycystin-2 (PC2) respectively. Although altered intracellular trafficking of PC1 and PC2 appear as an underlying feature of ADPKD, the mechanisms which govern vesicular transport of the polycystins through the biosynthetic and endosomal membrane networks remain to be fully elucidated...
May 3, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29724821/phosphoinositide-interacting-regulator-of-trp-pirt-has-opposing-effects-on-human-and-mouse-trpm8-ion-channels
#12
Jacob K Hilton, Taraneh Salehpour, Nicholas J Sisco, Parthasarathi Rath, Wade D Van Horn
Transient receptor potential melastatin 8 (TRPM8) is a cold-sensitive ion channel with diverse physiological roles. TRPM8 activity is modulated by many mechanisms, including an interaction with the small membrane protein phosphoinositide-interacting regulator of TRP (PIRT). Here, using comparative electrophysiology experiments, we identified species-dependent differences between the human and mouse TRPM8-PIRT complexes. We found that human PIRT attenuated human TPRM8 conductance, unlike mouse PIRT, which enhanced mouse TRPM8 conductance...
May 3, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29721607/hydrogen-sulphide-facilitates-exocytosis-by-regulating-the-handling-of-intracellular-calcium-by-chromaffin-cells
#13
Ricardo de Pascual, Andrés M Baraibar, Iago Méndez-López, Martín Pérez-Ciria, Ignacio Polo-Vaquero, Luis Gandía, Sunny E Ohia, Antonio G García, Antonio M G de Diego
Gasotransmitter hydrogen sulphide (H2 S) has emerged as a regulator of multiple physiological and pathophysiological processes throughout. Here, we have investigated the effects of NaHS (fast donor of H2 S) and GYY4137 (GYY, slow donor of H2 S) on the exocytotic release of catecholamines from fast-perifused bovine adrenal chromaffin cells (BCCs) challenged with sequential intermittent pulses of a K+ -depolarizing solution. Both donors caused a concentration-dependent facilitation of secretion. This was not due to an augmentation of Ca2+ entry through voltage-activated Ca2+ channels (VACCs) because, in fact, NaHS and GYY caused a mild inhibition of whole-cell Ca2+ currents...
May 2, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29705952/phosphatidylinositol-3-5-bisphosphate-lipid-binding-induced-activation-of-the-human-two-pore-channel-2
#14
Sonja A Kirsch, Andreas Kugemann, Armando Carpaneto, Rainer A Böckmann, Petra Dietrich
Mammalian two-pore channels (TPCs) are activated by the low-abundance membrane lipid phosphatidyl-(3,5)-bisphosphate (PI(3,5)P2 ) present in the endo-lysosomal system. Malfunction of human TPC1 or TPC2 (hTPC) results in severe organellar storage diseases and membrane trafficking defects. Here, we compared the lipid-binding characteristics of hTPC2 and of the PI(3,5)P2 -insensitive TPC1 from the model plant Arabidopsis thaliana. Combination of simulations with functional analysis of channel mutants revealed the presence of an hTPC2-specific lipid-binding pocket mutually formed by two channel regions exposed to the cytosolic side of the membrane...
April 28, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29694233/functional-features-of-the-finger-domain-of-deg-enac-channels-mec-4-and-unc-8
#15
Cristina Matthewman, Christina K Johnson, David M Miller Iii, Laura Bianchi
UNC-8 and MEC-4 are two members of the DEG/ENaC family of voltage-independent Na+ channels that share a high degree of sequence homology and functional similarity. For example, both can be hyperactivated by genetic mutations (UNC-8(d) and MEC-4(d)) that induce neuronal death by necrosis. Both depend in vivo on chaperone protein MEC-6 for function, as demonstrated by the finding that neuronal death induced by hyperactive UNC-8 and MEC-4 channels is prevented by null mutations in mec-6. UNC-8 and MEC-4 differ functionally in three major ways: 1) MEC-4 is calcium permeable whereas UNC-8 is not; 2) UNC-8, but not MEC-4, is blocked by extracellular calcium and magnesium in the micromolar range; 3) MEC-6 increases the number of MEC-4 channels at the cell surface in oocytes but does not have this effect on UNC-8...
April 25, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29680149/recent-progress-in-the-discovery-and-development-of-small-molecule-modulators-of-cftr
#16
Phil R Kym, Xueqing Wang, Mathieu Pizzonero, Steven E Van der Plas
Cystic fibrosis (CF) is a genetic disorder driven by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. While different mutations lead to varying levels of disease severity, the most common CFTR F508del mutation leads to defects in protein stability, trafficking to the cell membrane and gating of chloride ions. Recently, advances in medicinal chemistry have led to the identification small-molecule drugs that result in significant clinical efficacy in improving lung function in CF patients...
2018: Progress in Medicinal Chemistry
https://www.readbyqxmd.com/read/29675583/do-alcohol-related-ampa-type-glutamate-receptor-adaptations-promote-intake
#17
F Woodward Hopf, Regina A Mangieri
Ionotropic glutamate receptors (AMPA, NMDA, and kainate receptors) play a central role in excitatory glutamatergic signaling throughout the brain. As a result, functional changes, especially long-lasting forms of plasticity, have the potential to profoundly alter neuronal function and the expression of adaptive and pathological behaviors. Thus, alcohol-related adaptations in ionotropic glutamate receptors are of great interest, since they could promote excessive alcohol consumption, even after long-term abstinence...
April 20, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29674316/activation-of-renal-clc-k-chloride-channels-depends-on-an-intact-n-terminus-of-their-accessory-subunit-barttin
#18
Daniel Wojciechowski, Stefan Thiemann, Christina Schaal, Alina Rahtz, Jeanne de la Roche, Birgit Begemann, Toni Becher, Martin Fischer
ClC-K channels belong to the CLC family of chloride channels and chloride/proton antiporters. They contribute to sodium chloride reabsorption in Henle's loop of the kidney and to potassium secretion into the endolymph by the stria vascularis of the inner ear. Their accessory subunit barttin stabilizes the ClC-K/barttin complex, promotes its insertion into the surface membrane, and turns the pore-forming subunits into a conductive state. Barttin mutations cause Bartter syndrome type IV, a salt wasting nephropathy with sensorineural deafness...
April 19, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29665816/selective-localization-of-igg-from-cerebrospinal-fluid-to-brain-parenchyma
#19
Marlene Thorsen Mørch, Sofie Forsberg Sørensen, Reza Khorooshi, Nasrin Asgari, Trevor Owens
BACKGROUND: Encounter of autoantibodies with specific antigens can lead to hypersensitivity reactions and pathology. In multiple sclerosis and neuromyelitis optica spectrum disease (NMOSD), immunoglobulin-G (IgG) deposition has been observed in pathological lesions in the central nervous system. The paradigmatic autoantibodies in NMOSD are specific for the water channel aquaporin-4, localized to astrocytic end-feet at the blood-brain barrier and ependymal cells at the cerebrospinal fluid-brain barrier...
April 17, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29650988/the-c-terminal-hret-sequence-of-kv1-3-regulates-gating-rather-than-targeting-of-kv1-3-to-the-plasma-membrane
#20
Orsolya Voros, Orsolya Szilagyi, András Balajthy, Sándor Somodi, Gyorgy Panyi, Péter Hajdu
Kv1.3 channels are expressed in several cell types including immune cells, such as T lymphocytes. The targeting of Kv1.3 to the plasma membrane is essential for T cell clonal expansion and assumed to be guided by the C-terminus of the channel. Using two point mutants of Kv1.3 with remarkably different features compared to the wild-type Kv1.3 (A413V and H399K having fast inactivation kinetics and tetraethylammonium-insensitivity, respectively) we showed that both Kv1.3 channel variants target to the membrane when the C-terminus was truncated right after the conserved HRET sequence and produce currents identical to those with a full-length C-terminus...
April 12, 2018: Scientific Reports
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