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https://www.readbyqxmd.com/read/28054303/amino-acid-properties-of-trafficking-determinants-in-the-outer-pore-forming-region-of-kv1-potassium-channels-in-cell-lines
#1
Barbara Gomez, Jing Zhu, Esperanza Recio-Pinto, William B Thornhill
Different classes of Kv1 potassium channels have different trafficking patterns despite having very similar amino acid sequences. Two amino acids responsible for these differences have been identified in the outer pore turret region of Kv1.1 and Kv1.4. Here we tested a series of substitutions at these two determinants on Kv1.4. All P506 substitutions tested resulted in a significant decrease in surface protein, total protein, and protein half-life, indicating that proline is required at 506 to stabilize protein conformation and increase trafficking to the cell surface...
January 5, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28034367/dendritic-trafficking-faces-physiologically-critical-speed-precision-tradeoffs
#2
Alex H Williams, Cian O'Donnell, Terrence J Sejnowski, Timothy O'Leary
Nervous system function requires intracellular transport of channels, receptors, mRNAs, and other cargo throughout complex neuronal morphologies. Local signals such as synaptic input can regulate cargo trafficking, motivating the leading conceptual model of neuron-wide transport, sometimes called the 'sushi-belt model' (Doyle and Kiebler, 2011). Current theories and experiments are based on this model, yet its predictions are not rigorously understood. We formalized the sushi belt model mathematically, and show that it can achieve arbitrarily complex spatial distributions of cargo in reconstructed morphologies...
December 30, 2016: ELife
https://www.readbyqxmd.com/read/28028442/regulation-of-vdac-trafficking-modulates-cell-death
#3
Ashvini K Dubey, Ashwini Godbole, M K Mathew
The voltage-dependent anion channel (VDAC) and mitochondria-associated hexokinase (HxK) have crucial roles in both cell survival and death. Both the individual abundances and their ratio seem to influence the balance of survival and death and are thus critical in scenarios, such as neurodegeneration and cancer. Elevated levels of both VDAC and HxK have been reported in cancerous cells. Physical interaction is surmised and specific residues or regions involved have been identified, but details of the interaction and the mechanism by which it modulates survival are yet to be elucidated...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/28001373/direct-measurement-of-trafficking-of-the-cystic-fibrosis-transmembrane-conductance-regulator-to-the-cell-surface-and-binding-to-a-chemical-chaperone
#4
Zhihui Zhang, Michael M Baksh, M G Finn, David K Heidary, Christopher I Richards
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) result in the disease cystic fibrosis. Deletion of Phe508, the most prevalent mutation associated with this disease, disrupts trafficking of the protein. Small molecule correctors yield moderate improvements in the trafficking of ΔF508-CFTR to the plasma membrane. It is currently not known if correctors increase the level of trafficking through improved cargo loading of transport vesicles or through direct binding to CFTR. Real-time measurements of trafficking were utilized to identify the mechanistic details of chemical, biochemical, and thermal factors that impact CFTR correction, using the corrector molecule VX-809, a secondary mutation (I539T), and low-temperature conditions...
December 21, 2016: Biochemistry
https://www.readbyqxmd.com/read/27998983/bag1-promotes-trc8-dependent-degradation-of-misfolded-herg-potassium-channels
#5
Christine Hantouche, Brittany Williamson, William C Valinsky, Joshua Solomon, Alvin Shrier, Jason C Young
Cardiac long QT syndrome type 2 is caused by mutations in the hERG potassium channel, many of which cause misfolding and degradation at the endoplasmic reticulum, instead of normal trafficking to the cell surface. The Hsc70/Hsp70 chaperones assist the folding of the hERG cytosolic domains. Here, we demonstrate that the Hsp70 nucleotide exchange factor Bag1 promotes hERG degradation by the ubiquitin-proteasome system at the endoplasmic reticulum, to regulate hERG levels and channel activity. Dissociation of hERG complexes containing Hsp70 and the E3 ubiquitin ligase CHIP requires the interaction of Bag1 with Hsp70 but this does not involve the Bag1 ubiquitin-like domain...
December 20, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27994149/fgf14-is-a-regulator-of-kcnq2-3-channels
#6
Juan Lorenzo Pablo, Geoffrey S Pitt
KCNQ2/3 (Kv7.2/7.3) channels and voltage-gated sodium channels (VGSCs) are enriched in the axon initial segment (AIS) where they bind to ankyrin-G and coregulate membrane potential in central nervous system neurons. The molecular mechanisms supporting coordinated regulation of KCNQ and VGSCs and the cellular mechanisms governing KCNQ trafficking to the AIS are incompletely understood. Here, we show that fibroblast growth factor 14 (FGF14), previously described as a VGSC regulator, also affects KCNQ function and localization...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27986285/methods-for-monitoring-ca-2-and-ion-channels-in-the-lysosome
#7
REVIEW
Xi Zoë Zhong, Yiming Yang, Xue Sun, Xian-Ping Dong
Lysosomes and lysosome-related organelles are emerging as intracellular Ca(2+) stores and play important roles in a variety of membrane trafficking processes, including endocytosis, exocytosis, phagocytosis and autophagy. Impairment of lysosomal Ca(2+) homeostasis and membrane trafficking has been implicated in many human diseases such as lysosomal storage diseases (LSDs), neurodegeneration, myopathy and cancer. Lysosomal membrane proteins, in particular ion channels, are crucial for lysosomal Ca(2+) signaling...
December 9, 2016: Cell Calcium
https://www.readbyqxmd.com/read/27964885/membrane-protein-trafficking-in-drosophila-photoreceptor-cells
#8
REVIEW
Krystina Schopf, Armin Huber
Membrane protein trafficking occurs throughout the lifetime of neurons and includes the initial protein synthesis and anterograde transport to the plasma membrane as well as internalization, degradation, and recycling of plasma membrane proteins. Defects in protein trafficking can result in neuronal degeneration and underlie blinding diseases such as retinitis pigmentosa as well as other neuronal disorders. Drosophila photoreceptor cells have emerged as a model system for identifying the components and mechanisms involved in membrane protein trafficking in neurons...
December 7, 2016: European Journal of Cell Biology
https://www.readbyqxmd.com/read/27956381/hydrogen-peroxide-suppresses-trpm4-trafficking-to-the-apical-membrane-in-mouse-cortical-collecting-duct-principal-cells
#9
Ming-Ming Wu, Yu-Jia Zhai, Yu-Xia Li, Qing-Qing Hu, Zhi-Rui Wang, Shi-Peng Wei, Li Zou, Abdel A Alli, Tiffany L Thai, Zhi-Ren Zhang, He-Ping Ma
A Ca(2+)-activated nonselective cation channel (NSCCa) is found in principal cells of the mouse cortical collecting duct (CCD). However, the molecular identity of this channel remains unclear. We used mpkCCDc14 cells, a mouse CCD principal cell line, to determine whether NSCCa represents the transient receptor potential (TRP) channel, the melastatin subfamily 4 (TRPM4). A Ca(2+)-sensitive single-channel current was observed in inside-out patches excised from the apical membrane of mpkCCDc14 cells. Like TRPM4 channels found in other cell types, this channel has an equal permeability for Na(+) and K(+) and has a linear current-voltage relationship with a slope conductance of ~23 pS...
December 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27941029/deubiquitylating-enzymes-in-receptor-endocytosis-and-trafficking
#10
REVIEW
Aidan P McCann, Christopher J Scott, Sandra Van Schaeybroeck, James F Burrows
In recent times, our knowledge of the roles ubiquitin plays in multiple cellular processes has expanded exponentially, with one example being the role of ubiquitin in receptor endocytosis and trafficking. This has prompted a multitude of studies examining how the different machinery involved in the addition and removal of ubiquitin can influence this process. Multiple deubiquitylating enzymes (DUBs) have been implicated either in facilitating receptor endocytosis and lysosomal degradation or in rescuing receptor levels by preventing endocytosis and/or promoting recycling to the plasma membrane...
December 15, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27940916/hierarchical-crmp2-posttranslational-modifications-control-nav1-7-function
#11
Erik T Dustrude, Aubin Moutal, Xiaofang Yang, Yuying Wang, May Khanna, Rajesh Khanna
Voltage-gated sodium channels are crucial determinants of neuronal excitability and signaling. Trafficking of the voltage-gated sodium channel NaV1.7 is dysregulated in neuropathic pain. We identify a trafficking program for NaV1.7 driven by hierarchical interactions with posttranslationally modified versions of the binding partner collapsin response mediator protein 2 (CRMP2). The binding described between CRMP2 and NaV1.7 was enhanced by conjugation of CRMP2 with small ubiquitin-like modifier (SUMO) and further controlled by the phosphorylation status of CRMP2...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27938668/cellular-encoding-of-cy-dyes-for-single-molecule-imaging
#12
Lilia Leisle, Rahul Chadda, John D Lueck, Daniel T Infield, Jason D Galpin, Venkatramanan Krishnamani, Janice L Robertson, Christopher A Ahern
A general method is described for the site-specific genetic encoding of cyanine dyes as non-canonical amino acids (Cy-ncAAs) into proteins. The approach relies on an improved technique for nonsense suppression with in vitro misacylated orthogonal tRNA. The data show that Cy-ncAAs (based on Cy3 and Cy5) are tolerated by the eukaryotic ribosome in cell-free and whole-cell environments and can be incorporated into soluble and membrane proteins. In the context of the Xenopus laevis oocyte expression system, this technique yields ion channels with encoded Cy-ncAAs that are trafficked to the plasma membrane where they display robust function and distinct fluorescent signals as detected by TIRF microscopy...
December 12, 2016: ELife
https://www.readbyqxmd.com/read/27932395/ubiquitination-and-the-regulation-of-membrane-proteins
#13
REVIEW
Natalie Foot, Tanya Henshall, Sharad Kumar
Newly synthesized transmembrane proteins undergo a series of steps to ensure that only the required amount of correctly folded protein is localized to the membrane. The regulation of protein quality and its abundance at the membrane are often controlled by ubiquitination, a multistep enzymatic process that results in the attachment of ubiquitin, or chains of ubiquitin to the target protein. Protein ubiquitination acts as a signal for sorting, trafficking, and the removal of membrane proteins via endocytosis, a process through which multiple ubiquitin ligases are known to specifically regulate the functions of a number of ion channels, transporters, and signaling receptors...
January 2017: Physiological Reviews
https://www.readbyqxmd.com/read/27925199/dopamine-dependent-effects-on-basal-and-glutamate-stimulated-network-dynamics-in-cultured-hippocampal-neurons
#14
Yan Li, Xin Chen, Rhonda Dzakpasu, Katherine Conant
Oscillatory activity occurs in cortical and hippocampal networks with specific frequency ranges thought to be critical to working memory, attention, differentiation of neuronal precursors, and memory trace replay. Synchronized activity within relatively large neuronal populations is influenced by firing and bursting frequency within individual cells, and the latter is modulated by changes in intrinsic membrane excitability and synaptic transmission. Published work suggests that dopamine (DA), a potent modulator of learning and memory, acts on dopamine receptor 1-like dopamine receptors (D1Rs) to influence the phosphorylation and trafficking of glutamate receptor subunits, along with long-term potentiation (LTP) of excitatory synaptic transmission in striatum and prefrontal cortex...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27915047/physical-and-functional-interaction-of-snapin-with-cav1-3-calcium-channel-impacts-channel-protein-trafficking-in-atrial-myocytes
#15
Xiao-Li Sun, Ju-Fang Yuan, Tao Jin, Xiao-Qing Cheng, Qiang Wang, Jia Guo, Wei Zhang, Yin Zhang, Ling Lu, Zhao Zhang
The L-type Ca(2+) channel (LTCC) Cav1.3 plays a critical role in generating electrical activity in atrial myocytes and cardiac pacemaker cells. However, the molecular and functional basis of Cav1.3 modulation in atrial myocytes has not yet been fully understood. By using the yeast two-hybrid system (Y2H), a Cav1.3-associated protein was screened, which was identified as Snapin. Physical interaction and co-localization between Snapin and Cav1.3 were then confirmed in both the heterologous expression system and mouse atrial myocytes...
January 2017: Cellular Signalling
https://www.readbyqxmd.com/read/27905440/organization-and-functions-of-mglu-and-gabab-receptor-complexes
#16
Jean-Philippe Pin, Bernhard Bettler
The neurotransmitters glutamate and γ-aminobutyric acid (GABA) transmit synaptic signals by activating fast-acting ligand-gated ion channels and more slowly acting G-protein-coupled receptors (GPCRs). The GPCRs for these neurotransmitters, metabotropic glutamate (mGlu) and GABAB receptors, are atypical GPCRs with a large extracellular domain and a mandatory dimeric structure. Recent studies have revealed how these receptors are activated through multiple allosteric interactions between subunit domains. It emerges that the molecular complexity of these receptors is further increased through association with trafficking, effector and regulatory proteins...
December 1, 2016: Nature
https://www.readbyqxmd.com/read/27900370/a-patient-with-multisystem-dysfunction-carries-a-truncation-mutation-in-human-slc12a2-the-gene-encoding-the-na-k-2cl-cotransporter-nkcc1
#17
Eric Delpire, Lynne Wolfe, Bianca Flores, Rainelli Koumangoye, Cara C Schornak, Salma Omer, Barbara Pusey, Christopher Lau, Thomas Markello, David R Adams
This study describes a 13-yr-old girl with orthostatic intolerance, respiratory weakness, multiple endocrine abnormalities, pancreatic insufficiency, and multiorgan failure involving the gut and bladder. Exome sequencing revealed a de novo, loss-of-function allele in SLC12A2, the gene encoding the Na-K-2Cl cotransporter-1. The 11-bp deletion in exon 22 results in frameshift (p.Val1026Phefs*2) and truncation of the carboxy-terminal tail of the cotransporter. Preliminary studies in heterologous expression systems demonstrate that the mutation leads to a nonfunctional transporter, which is expressed and trafficked to the plasma membrane alongside wild-type NKCC1...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27893774/multivalent-interactions-of-human-primary-amine-oxidase-with-the-v-and-c22-domains-of-sialic-acid-binding-immunoglobulin-like-lectin-9-regulate-its-binding-and-amine-oxidase-activity
#18
Heli Elovaara, Vimal Parkash, Ruth Fair-Mäkelä, Outi M H Salo-Ahen, Gabriela Guédez, Eva Bligt-Lindén, Janne Grönholm, Sirpa Jalkanen, Tiina A Salminen
Sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) on leukocyte surface is a counter-receptor for endothelial cell surface adhesin, human primary amine oxidase (hAOC3), a target protein for anti-inflammatory agents. This interaction can be used to detect inflammation and cancer in vivo, since the labeled peptides derived from the second C2 domain (C22) of Siglec-9 specifically bind to the inflammation-inducible hAOC3. As limited knowledge on the interaction between Siglec-9 and hAOC3 has hampered both hAOC3-targeted drug design and in vivo imaging applications, we have now produced and purified the extracellular region of Siglec-9 (Siglec-9-EC) consisting of the V, C21 and C22 domains, modeled its 3D structure and characterized the hAOC3-Siglec-9 interactions using biophysical methods and activity/inhibition assays...
2016: PloS One
https://www.readbyqxmd.com/read/27892464/wnt5a-induces-renal-aqp2-expression-by-activating-calcineurin-signalling-pathway
#19
Fumiaki Ando, Eisei Sohara, Tetsuji Morimoto, Naofumi Yui, Naohiro Nomura, Eriko Kikuchi, Daiei Takahashi, Takayasu Mori, Alain Vandewalle, Tatemitsu Rai, Sei Sasaki, Yoshiaki Kondo, Shinichi Uchida
Heritable nephrogenic diabetes insipidus (NDI) is characterized by defective urine concentration mechanisms in the kidney, which are mainly caused by loss-of-function mutations in the vasopressin type 2 receptor. For the treatment of heritable NDI, novel strategies that bypass the defective vasopressin type 2 receptor are required to activate the aquaporin-2 (AQP2) water channel. Here we show that Wnt5a regulates AQP2 protein expression, phosphorylation and trafficking, suggesting that Wnt5a is an endogenous ligand that can regulate AQP2 without the activation of the classic vasopressin/cAMP signalling pathway...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27888388/cardiac-bin1-cbin1-is-a-regulator-of-cardiac-contractile-function-and-an-emerging-biomarker-of-heart-muscle-health
#20
REVIEW
Kang Zhou, Tingting Hong
In recent decades, a cardiomyocyte membrane scaffolding protein bridging integrator 1 (BIN1) has emerged as a critical multifunctional regulator of transverse-tubule (t-tubule) function and calcium signaling in cardiomyocytes. Encoded by a single gene with 20 exons that are alternatively spliced, more than ten BIN1 protein isoforms are expressed with tissue and disease specificity. The recently discovered cardiac alternatively spliced isoform BIN1 (cBIN1 or BIN1+13+17) plays a crucial role in organizing membrane microfolds within cardiac t-tubules...
November 23, 2016: Science China. Life Sciences
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