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https://www.readbyqxmd.com/read/28346775/hyperinsulinism-causing-mutations-cause-multiple-molecular-defects-in-sur1-nbd1
#1
Claudia Paola Alvarez, Marijana Stagljar, D Ranjith Muhandiram, Voula Kanelis
The sulfonylurea receptor 1 (SUR1) protein forms the regulatory subunit in ATP sensitive K+ (KATP) channels in the pancreas. SUR proteins are members of the ATP-binding cassette (ABC) superfamily of proteins. Binding and hydrolysis of MgATP at the SUR nucleotide binding domains (NBDs) lead to channel opening. Pancreatic KATP channels play an important role in insulin secretion. SUR1 mutations that result in increased channel opening ultimately inhibit insulin secretion and lead to neonatal diabetes. In contrast, SUR1 mutations that disrupt trafficking and/or decrease gating of KATP channels cause congenital hyperinsulinism, where over secretion of insulin occurs even in the presence of low glucose...
March 27, 2017: Biochemistry
https://www.readbyqxmd.com/read/28346351/in-vitro-and-in-vivo-studies-on-the-structural-organization-of-chs3-from-saccharomyces-cerevisiae
#2
Simon Gohlke, Subbaratnam Muthukrishnan, Hans Merzendorfer
Chitin biosynthesis in yeast is accomplished by three chitin synthases (Chs) termed Chs1, Chs2 and Chs3, of which the latter accounts for most of the chitin deposited within the cell wall. While the overall structures of Chs1 and Chs2 are similar to those of other chitin synthases from fungi and arthropods, Chs3 lacks some of the C-terminal transmembrane helices raising questions regarding its structure and topology. To fill this gap of knowledge, we performed bioinformatic analyses and protease protection assays that revealed significant information about the catalytic domain, the chitin-translocating channel and the interfacial helices in between...
March 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28342889/heteromeric-complexes-of-aldo-keto-reductase-auxiliary-kv%C3%AE-subunits-akr6a-regulate-sarcolemmal-localization-of-kv1-5-in-coronary-arterial-myocytes
#3
Matthew A Nystoriak, Deqing Zhang, Ganapathy Jagatheesan, Aruni Bhatnagar
Redox-sensitive potassium channels consisting of the voltage-gated K(+) (KV) channel pore subunit KV1.5 regulate resting membrane potential and thereby contractility of vascular smooth muscle cells. Members of the KV1 family associate with cytosolic auxiliary β subunits, which are members of the aldo-keto reductase (AKR) superfamily (AKR6A subfamily). The Kvβ subunits have been proposed to regulate Kv1 gating via pyridine nucleotide cofactor binding. However, the molecular identity of KVβ subunits that associate with native KV1...
March 22, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28342809/identity-and-function-of-a-cardiac-mitochondrial-small-conductance-ca-2-activated-k-channel-splice-variant
#4
Meiying Yang, Amadou K S Camara, Mohammed Aldakkak, Wai-Meng Kwok, David F Stowe
We provide evidence for location and function of a small conductance, Ca(2+)-activated K(+) (SKCa) channel isoform 3 (SK3) in mitochondria (m) of guinea pig, rat and human ventricular myocytes. SKCa agonists protected isolated hearts and mitochondria against ischemia/reperfusion (IR) injury; SKCa antagonists worsened IR injury. Intravenous infusion of a SKCa channel agonist/antagonist, respectively, in intact rats was effective in reducing/enhancing regional infarct size induced by coronary artery occlusion...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28331084/structural-insights-into-emerging-pediatric-pathogens-human-bocaparvoviruses
#5
Mario Mietzsch, Shweta Kailasan, Jamie Garrison, Maria Ilyas, Paul Chipman, Kalle Kantola, Mandy E Janssen, John Spear, Duncan Sousa, Robert McKenna, Kevin Brown, Maria Söderlund-Venermo, Timothy Baker, Mavis Agbandje-McKenna
Bocaparvoviruses are emerging pathogens of the Parvoviridae family. Human bocaviruses 1 (HBoV1) causes severe respiratory infections and HBoV2-4 gastrointestinal infections in young children. Recent reports of life threatening cases, lack of direct treatment or vaccination, and a limited understanding of their disease mechanisms demand the need to study these pathogens on a molecular and structural level for the development of therapeutics. Towards this end, the capsid structures of HBoV1, HBoV3, and HBoV4 were determined to 2...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28322444/identification-and-characterization-of-site-specific-n-glycosylation-in-the-potassium-channel-kv3-1b
#6
Paul Christian Vicente, Jin Young Kim, Jeong-Ju Ha, Min-Young Song, Hyun-Kyung Lee, Dong-Hyun Kim, Jin-Sung Choi, Kang-Sik Park
The potassium ion channel Kv3.1b is a member of a family of voltage-gated ion channels that are glycosylated in their mature form. In the present study, we demonstrate the impact of N-glycosylation at specific asparagine residues on the trafficking of the Kv3.1b protein. Large quantities of asparagine 229 (N229)-glycosylated Kv3.1b reached the plasma membrane, whereas N220-glycosylated and unglycosylated Kv3.1b were mainly retained in the endoplasmic reticulum (ER). These ER-retained Kv3.1b proteins were susceptible to degradation when co-expressed with calnexin, whereas Kv3...
March 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28294298/proteins-and-chemical-chaperones-involved-in-neuronal-nicotinic-receptor-expression-and-function-an-update
#7
REVIEW
Arianna Crespi, Sara Francesca Colombo, Cecilia Gotti
Neuronal nicotinic acetylcholine receptors (nAChRs) are a family of acetylcholine-(ACh) gated cation channels and their homeostasis or proteostasis is essential for the correct physiology of the central and peripheral nervous systems. The proteostasis network regulates the folding, assembly, degradation and trafficking of nAChRs in order to ensure their efficient functional cell surface expression. However, as nAChRs are multisubunit, multispan, integral membrane proteins, the folding and assembly is a very inefficient process, and only a small portion of subunits can form functional pentamers...
March 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28279657/transcriptional-and-post-translational-regulation-of-pannexins
#8
REVIEW
Andrew K J Boyce, Anna L Epp, Archana Nagarajan, Leigh Anne Swayne
Pannexins are a 3-membered family of proteins that form large pore ion and metabolite channels in vertebrates. The impact of pannexins on vertebrate biology is intricately tied to where and when they are expressed, and how they are modified, once produced. The purpose of this review is therefore to outline our current understanding of transcriptional and post-translational regulation of pannexins. First, we briefly summarize their discovery and characteristics. Next, we describe several aspects of transcriptional regulation, including cell and tissue-specific expression, dynamic expression over development and disease, as well as new insights into the underlying molecular machinery involved...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28277940/a-single-structurally-conserved-sumoylation-site-in-crmp2-controls-nav1-7-function
#9
Erik Thomas Dustrude, Samantha Perez-Miller, Liberty François-Moutal, Aubin Moutal, May Khanna, Rajesh Khanna
The neuronal collapsin response mediator protein 2 (CRMP2) undergoes several posttranslational modifications that codify its functions. Most recently, CRMP2 SUMOylation (addition of small ubiquitin like modifier (SUMO)) was identified as a key regulatory step within a modification program that codes for CRMP2 interaction with, and trafficking of, voltage-gated sodium channel NaV1.7. In this paper, we illustrate the utility of combining sequence alignment within protein families with structural analysis to identify, from several putative SUMOylation sites, those that are most likely to be biologically relevant...
February 28, 2017: Channels
https://www.readbyqxmd.com/read/28265686/inhibition-of-cloned-herg-potassium-channels-by-risperidone-and-paliperidone
#10
Hong Joon Lee, Jin-Sung Choi, Bok Hee Choi, Sang June Hahn
Risperidone and one of its active metabolites, paliperidone, are widely used for the treatment of schizophrenia. We used a patch-clamp study to investigate the effects of paliperidone on hERG potassium channels expressed in HEK cells. Western blot analyses were used to study the effects of risperidone and paliperidone on hERG and hERG 3.1 isoform channel trafficking. Risperidone and paliperidone inhibited the hERG tail currents in a concentration-dependent manner with IC50 values of 0.16 and 0.57 μM, respectively...
March 6, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28258563/molecular-biology-of-aquaporins
#11
Chunling Li, Weidong Wang
Aquaporins (AQPs ) are a family of membrane water channels that basically function as regulators of intracellular and intercellular water flow. To date, thirteen AQPs , which are distributed widely in specific cell types in various organs and tissues, have been characterized in humans. Four AQP monomers, each of which consists of six membrane-spanning alpha-helices that have a central water-transporting pore, assemble to form tetramers, forming the functional units in the membrane. AQP facilitates osmotic water transport across plasma membranes and thus transcellular fluid movement...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28257070/plasmodesmata-mediated-cell-to-cell-communication-in-the-shoot-apical-meristem-how-stem-cells-talk
#12
REVIEW
Munenori Kitagawa, David Jackson
Positional information is crucial for the determination of plant cell fates, and it is established based on coordinated cell-to-cell communication, which in turn is essential for plant growth and development. Plants have evolved a unique communication pathway, with tiny channels called plasmodesmata (PD) spanning the cell wall. PD interconnect most cells in the plant and generate a cytoplasmic continuum, to mediate short- and long-distance trafficking of various molecules. Cell-to-cell communication through PD plays a role in transmitting positional signals, however, the regulatory mechanisms of PD-mediated trafficking are still largely unknown...
March 1, 2017: Plants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28256585/lrp1-influences-trafficking-of-n-type-calcium-channels-via-interaction-with-the-auxiliary-%C3%AE-2%C3%AE-1-subunit
#13
Ivan Kadurin, Simon W Rothwell, Beatrice Lana, Manuela Nieto-Rostro, Annette C Dolphin
Voltage-gated Ca(2+) (CaV) channels consist of a pore-forming α1 subunit, which determines the main functional and pharmacological attributes of the channel. The CaV1 and CaV2 channels are associated with auxiliary β- and α2δ-subunits. The molecular mechanisms involved in α2δ subunit trafficking, and the effect of α2δ subunits on trafficking calcium channel complexes remain poorly understood. Here we show that α2δ-1 is a ligand for the Low Density Lipoprotein (LDL) Receptor-related Protein-1 (LRP1), a multifunctional receptor which mediates trafficking of cargoes...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28246186/regulation-of-transporters-and-channels-by-membrane-trafficking-complexes-in-epithelial-cells
#14
Curtis T Okamoto
The vectorial secretion and absorption of fluid and solutes by epithelial cells is dependent on the polarized expression of membrane solute transporters and channels at the apical and basolateral membranes. The establishment and maintenance of this polarized expression of transporters and channels are affected by divers protein-trafficking complexes. Moreover, regulation of the magnitude of transport is often under control of physiological stimuli, again through the interaction of transporters and channels with protein-trafficking complexes...
February 28, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28238551/molecular-mechanism-of-ampa-receptor-modulation-by-tarp-stargazin
#15
Anat Ben-Yaacov, Moshe Gillor, Tomer Haham, Alon Parsai, Mohammad Qneibi, Yael Stern-Bach
AMPA receptors (AMPARs) mediate the majority of fast excitatory transmission in the brain and critically contribute to synaptic plasticity and pathology. AMPAR trafficking and gating are tightly controlled by auxiliary transmembrane AMPAR regulatory proteins (TARPs). Here, using systematic domain swaps with the TARP-insensitive kainate receptor GluK2, we show that AMPAR interaction with the prototypical TARP stargazin/γ2 primarily involves the AMPAR membrane domains M1 and M4 of neighboring subunits, initiated or stabilized by the AMPAR C-tail, and that these interactions are sufficient to enable full receptor modulation...
February 17, 2017: Neuron
https://www.readbyqxmd.com/read/28235863/normal-thymocyte-egress-t-cell-trafficking-and-cd4-t-cell-homeostasis-require-interactions-between-rgs-proteins-and-g%C3%AE-i2
#16
Il-Young Hwang, Chung Park, Kathleen Harrison, John H Kehrl
Adaptive immunity depends on mature thymocytes leaving the thymus to enter the bloodstream and the trafficking of T cells through lymphoid organs. Both of these require heterotrimeric Gαi protein signaling, whose intensity and duration are controlled by the regulator of G protein signaling (RGS) proteins. In this study, we show that RGS protein/Gαi2 interactions are essential for normal thymocyte egress, T cell trafficking, and homeostasis. Mature thymocytes with a Gαi2 mutation that disables RGS protein binding accumulated in the perivascular channels of thymic corticomedullary venules...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28235671/scn3a-deficiency-associated-with-increased-seizure-susceptibility
#17
Tyra Lamar, Carlos G Vanoye, Jeffrey Calhoun, Jennifer C Wong, Stacey B B Dutton, Benjamin S Jorge, Milen Velinov, Andrew Escayg, Jennifer A Kearney
Mutations in voltage-gated sodium channels expressed highly in the brain (SCN1A, SCN2A, SCN3A, and SCN8A) are responsible for an increasing number of epilepsy syndromes. In particular, mutations in the SCN3A gene, encoding the pore-forming Nav1.3 α subunit, have been identified in patients with focal epilepsy. Biophysical characterization of epilepsy-associated SCN3A variants suggests that both gain- and loss-of-function SCN3A mutations may lead to increased seizure susceptibility. In this report, we identified a novel SCN3A variant (L247P) by whole exome sequencing of a child with focal epilepsy, developmental delay, and autonomic nervous system dysfunction...
February 22, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28223936/two-pore-channels-catalyzers-of-endolysosomal-transport-and-function
#18
REVIEW
Christian Grimm, Cheng-Chang Chen, Christian Wahl-Schott, Martin Biel
Two-pore channels (TPCs) have recently emerged as a novel class of non-selective cation channels in the endolysosomal system. There are two members in the human genome, TPC1 and TPC2. Studies with TPC knockout and knockdown models have revealed that these channels participate in the regulation of multiple endolysosomal trafficking pathways which when dysregulated can lead to or influence the development of a range of different diseases such as lysosomal storage, metabolic, or infectious diseases. TPCs have been demonstrated to be activated by different endogenous stimuli, PI(3,5)P2 and NAADP, and ATP has been found to block TPC activation via mTOR...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28223219/trpm2-contributes-to-lpc-induced-intracellular-ca-2-influx-and-microglial-activation
#19
Heejin Jeong, Yong Ho Kim, Yunsin Lee, Sung Jun Jung, Seog Bae Oh
Microglia are the resident immune cells which become activated in some pathological conditions in central nervous system (CNS). Lysophosphatidylcholine (LPC), an endogenous inflammatory phospholipid, is implicated in immunomodulatory function of glial cells in the CNS. Although several studies uncovered that LPC induces intracellular Ca(2+) influx and morphologic change in microglia, there is still no direct evidence showing change of phosphorylation of mitogen-activated protein kinase (MAPK) p38 (p-p38), a widely used microglia activation marker, by LPC...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28221136/an-essential-dual-function-complex-mediates-erythrocyte-invasion-and-channel-mediated-nutrient-uptake-in-malaria-parasites
#20
Daisuke Ito, Marc A Schureck, Sanjay A Desai
Malaria parasites evade immune detection by growth and replication within erythrocytes. After erythrocyte invasion, the intracellular pathogen must increase host cell uptake of nutrients from plasma. Here, we report that the parasite-encoded RhopH complex contributes to both invasion and channel-mediated nutrient uptake. As rhoph2 and rhoph3 gene knockouts were not viable in the human P. falciparum pathogen, we used conditional knockdowns to determine that the encoded proteins are essential and to identify their stage-specific functions...
February 21, 2017: ELife
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