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https://www.readbyqxmd.com/read/27913662/direct-functional-interaction-of-the-kinesin-13-family-member-kinesin-like-protein-2a-kif2a-and-arf-gap-with-gtp-binding-protein-like-ankyrin-repeats-and-ph-domains-1-agap1
#1
Ruibai Luo, Pei-Wen Chen, Michael Wagenbach, Xiaoying Jian, Lisa Jenkins, Linda Wordeman, Paul A Randazzo
No abstract text is available yet for this article.
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27911898/bilaterian-giant-ankyrins-have-a-common-evolutionary-origin-and-play-a-conserved-role-in-patterning-the-axon-initial-segment
#2
Timothy Jegla, Michelle M Nguyen, Chengye Feng, Daniel J Goetschius, Esteban Luna, Damian B van Rossum, Bishoy Kamel, Aditya Pisupati, Elliott S Milner, Melissa M Rolls
In vertebrate neurons, the axon initial segment (AIS) is specialized for action potential initiation. It is organized by a giant 480 Kd variant of ankyrin G (AnkG) that serves as an anchor for ion channels and is required for a plasma membrane diffusion barrier that excludes somatodendritic proteins from the axon. An unusually long exon required to encode this 480Kd variant is thought to have been inserted only recently during vertebrate evolution, so the giant ankyrin-based AIS scaffold has been viewed as a vertebrate adaptation for fast, precise signaling...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27909246/retromer-wash-dependent-sorting-of-nutrient-transporters-requires-a-multivalent-interaction-network-with-ankrd50
#3
Arunas Kvainickas, Ana Jimenez Orgaz, Heike Nägele, Britta Diedrich, Kate J Heesom, Jörn Dengjel, Peter J Cullen, Florian Steinberg
Retromer and the associated actin polymerizing WASH-complex are essential for the endocytic recycling of a wide range of integral membrane proteins. A hereditary Parkinson's disease causing point mutation (D620N) in the retromer subunit VPS35 perturbs retromer's association with the WASH-complex and also with the uncharacterized protein Ankyrin Repeat Domain Containing Protein 50 (ANKRD50). Here, we firmly establish ANKRD50 as a novel and essential component of the SNX27-retromer-WASH supercomplex. Depletion of ANKRD50 in HeLa or U2OS cells phenocopied the loss of endosome to cell surface recycling of multiple transmembrane proteins seen upon suppression of SNX27, retromer or WASH-complex components...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27903800/genetic-variability-of-myxoma-virus-genomes
#4
Christoph Braun, Andrea Thürmer, Rolf Daniel, Anne-Kathrin Schultz, Ingo Bulla, Horst Schirrmeier, Dietmar Mayer, Andreas Neubert, Claus-Peter Czerny
: Myxomatosis is a recurrent problem on rabbit farms throughout Europe despite the success of vaccines. To identify gene variations of field and vaccine strains that may be responsible for changes in virulence, immunomodulation, and immunoprotection, the genomes of 6 Myxoma virus strains (MYXV) were sequenced: German field isolates Munich-1, FLI-H, 2604, 3207, vaccine strain MAV, and challenge strain ZA. The analyzed genomes ranged from 147.6 kb (strain MAV) to 161.8 kb (strain 3207) in size...
November 30, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27901114/genome-wide-diversity-and-association-mapping-for-capsaicinoids-and-fruit-weight-in-capsicum-annuum-l
#5
Padma Nimmakayala, Venkata L Abburi, Thangasamy Saminathan, Suresh B Alaparthi, Aldo Almeida, Brittany Davenport, Marjan Nadimi, Joshua Davidson, Krittika Tonapi, Lav Yadav, Sridhar Malkaram, Gopinath Vajja, Gerald Hankins, Robert Harris, Minkyu Park, Doil Choi, John Stommel, Umesh K Reddy
Accumulated capsaicinoid content and increased fruit size are traits resulting from Capsicum annuum domestication. In this study, we used a diverse collection of C. annuum to generate 66,960 SNPs using genotyping by sequencing. The study identified 1189 haplotypes containing 3413 SNPs. Length of individual linkage disequilibrium (LD) blocks varied along chromosomes, with regions of high and low LD interspersed with an average LD of 139 kb. Principal component analysis (PCA), Bayesian model based population structure analysis and an Euclidean tree built based on identity by state (IBS) indices revealed that the clustering pattern of diverse accessions are in agreement with capsaicin content (CA) and fruit weight (FW) classifications indicating the importance of these traits in shaping modern pepper genome...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899696/selective-antagonism-of-trpa1-produces-limited-efficacy-in-models-of-inflammatory-and-neuropathic-induced-mechanical-hypersensitivity-in-rats
#6
Sonya G Lehto, Andy D Weyer, Beth D Youngblood, Maosheng Zhang, Ruoyuan Yin, Weiya Wang, Yohannes Teffera, Melanie Cooke, Cheryl L Stucky, Laurie Schenkel, Stephanie Geuns-Meyer, Bryan D Moyer, Kenneth D Wild, Narender R Gavva
The transient receptor potential ankyrin 1 (TRPA1) channel has been implicated in pathophysiological processes that include asthma, cough, and inflammatory pain. Agonists of TRPA1 such as mustard oil and its key component allyl isothiocyanate (AITC) cause pain and neurogenic inflammation in humans and rodents, and TRPA1 antagonists have been reported to be effective in rodent models of pain. In our pursuit of TRPA1 antagonists as potential therapeutics, we generated AMG0902, a potent (IC90 of 300 nM against rat TRPA1), selective, brain penetrant (brain to plasma ratio of 0...
2016: Molecular Pain
https://www.readbyqxmd.com/read/27895120/ankyrin-g-expression-regulates-apical-delivery-of-the-epithelial-sodium-channel-enac
#7
Christine A Klemens, Robert S Edinger, Lindsay Kightlinger, Xiaoning Liu, Michael B Butterworth
The epithelial sodium channel (ENaC) is the limiting entry point for Na(+) reabsorption in the distal kidney nephron and is regulated by numerous hormones, including the mineralocorticoid hormone aldosterone. Previously we identified ankyrin G (AnkG), a cytoskeletal protein involved in vesicular transport, as a novel aldosterone-induced protein that can alter Na(+) transport in mouse cortical collecting duct (mCCD) cells. However, the mechanisms underlying AnkG's regulation of Na(+) transport were unknown. Here we report that AnkG expression directly regulates Na(+) transport by altering ENaC activity in the apical membrane...
November 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27881684/conformational-flexibility-of-an-anti-il-13-darpin%C3%A2
#8
Alexey Teplyakov, Thomas J Malia, Galina Obmolova, Steven A Jacobs, Karyn T O'Neil, Gary L Gilliland
Designed ankyrin repeat proteins (DARPin(®)) are artificial non-immunoglobulin binding proteins with potential applications as therapeutic molecules. DARPin 6G9 binds interleukin-13 with high affinity and blocks the signaling pathway and as such is promising for the treatment of asthma and other atopic diseases. The crystal structures of DARPin 6G9 in the unbound form and in complex with IL-13 were determined at high resolution. The DARPin competes for the same epitope as the IL-13 receptor chain 13Rα1 but does not interfere with the binding of the other receptor chain, IL-4Rα...
November 23, 2016: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/27875296/the-n-terminal-ankyrin-repeat-domain-is-not-required-for-electrophile-and-heat-activation-of-the-purified-mosquito-trpa1-receptor
#9
Sabeen Survery, Lavanya Moparthi, Per Kjellbom, Edward D Högestätt, Peter M Zygmunt, Urban Johanson
Temperature sensors are crucial for animals to optimize living conditions. The temperature response of the ion channel transient receptor potential A1 (TRPA1) is intriguing, some orthologs have been reported to be activated by cold and others by heat, but the molecular mechanisms responsible for its activation remain elusive. Single-channel electrophysiological recordings of heterologously expressed and purified Anopheles gambiae TRPA1 (AgTRPA1), with and without the N-terminal ankyrin repeat domain, demonstrate that both proteins are functional as they responded to the electrophilic compounds allyl isothiocyanate (AITC) and cinnamaldehyde as well as heat...
November 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27874100/structural-basis-of-trpa1-inhibition-by-hc-030031-utilizing-species-specific-differences
#10
Rupali Gupta, Shigeru Saito, Yoshiharu Mori, Satoru G Itoh, Hisashi Okumura, Makoto Tominaga
Pain is a harmful sensation that arises from noxious stimuli. Transient receptor potential ankyrin 1 (TRPA1) is one target for studying pain mechanisms. TRPA1 is activated by various stimuli such as noxious cold, pungent natural products and environmental irritants. Since TRPA1 is an attractive target for pain therapy, a few TRPA1 antagonists have been developed and some function as analgesic agents. The responses of TRPA1 to agonists and antagonists vary among species and these species differences have been utilized to identify the structural basis of activation and inhibition mechanisms...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27871938/the-role-of-gpi-anchored-axonal-glycoproteins-in-neural-development-and-neurological-disorders
#11
REVIEW
Gianfranco Gennarini, Antonella Bizzoca, Sabrina Picocci, Daniela Puzzo, Patrizia Corsi, Andrew J W Furley
This review article focuses on the Contactin (CNTN) subset of the Immunoglobulin supergene family (IgC2/FNIII molecules), whose components share structural properties (the association of Immunoglobulin type C2 with Fibronectin type III domains), as well as a general role in cell contact formation and axonal growth control. IgC2/FNIII molecules include 6 highly related components (CNTN 1-6), associated with the cell membrane via a Glycosyl Phosphatidyl Inositol (GPI)-containing lipid tail. Contactin 1 and Contactin 2 share ~50 (49...
November 18, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27871341/functional-analysis-of-a-nf-%C3%AE%C2%BAb-transcription-factor-in-the-immune-defense-of-oriental-fruit-fly-bactrocera-dorsalis-hendel-diptera-tephritidae
#12
Z Shi, H Liang, Y Hou
Although some novel antimicrobial peptides (AMP) have been successfully isolated from Bactrocera dorsalis Hendel, the mechanisms underlying the induction of these peptides are still elusive. The homolog of NF-κB transcription factor Relish, designated as BdRelish, was cloned from B. dorsalis. The full length cDNA of BdRelish is 3954 bp with an open reading frame that encodes 1013 amino acids. Similar to Drosophila Relish and the mammalian p100, it is a compound protein containing a conserved Rel homology domain, an IPT (Ig-like, plexins, transcription factors) domain and an IκB-like domain (four ankyrin repeats), the nuclear localization signal RKRRR is also detected at the residues 449-453, suggesting that it has homology to Relish and it is a member of the Rel family of transcription activator proteins...
November 22, 2016: Bulletin of Entomological Research
https://www.readbyqxmd.com/read/27863482/in-silico-snp-analysis-of-the-breast-cancer-antigen-ny-br-1
#13
Zeynep Kosaloglu, Julia Bitzer, Niels Halama, Zhiqin Huang, Marc Zapatka, Andreas Schneeweiss, Dirk Jäger, Inka Zörnig
BACKGROUND: Breast cancer is one of the most common malignancies with increasing incidences every year and a leading cause of death among women. Although early stage breast cancer can be effectively treated, there are limited numbers of treatment options available for patients with advanced and metastatic disease. The novel breast cancer associated antigen NY-BR-1 was identified by SEREX analysis and is expressed in the majority (>70%) of breast tumors as well as metastases, in normal breast tissue, in testis and occasionally in prostate tissue...
November 18, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27856737/global-transformation-of-erythrocyte-properties-via-engagement-of-an-sh2-like-sequence-in-band-3
#14
Estela Puchulu-Campanella, Francesco M Turrini, Yen-Hsing Li, Philip S Low
Src homology 2 (SH2) domains are composed of weakly conserved sequences of ∼100 aa that bind phosphotyrosines in signaling proteins and thereby mediate intra- and intermolecular protein-protein interactions. In exploring the mechanism whereby tyrosine phosphorylation of the erythrocyte anion transporter, band 3, triggers membrane destabilization, vesiculation, and fragmentation, we discovered a SH2 signature motif positioned between membrane-spanning helices 4 and 5. Evidence that this exposed cytoplasmic sequence contributes to a functional SH2-like domain is provided by observations that: (i) it contains the most conserved sequence of SH2 domains, GSFLVR; (ii) it binds the tyrosine phosphorylated cytoplasmic domain of band 3 (cdb3-PO4) with Kd = 14 nM; (iii) binding of cdb3-PO4 to erythrocyte membranes is inhibited both by antibodies against the SH2 signature sequence and dephosphorylation of cdb3-PO4; (iv) label transfer experiments demonstrate the covalent transfer of photoactivatable biotin from isolated cdb3-PO4 (but not cdb3) to band 3 in erythrocyte membranes; and (v) phosphorylation-induced binding of cdb3-PO4 to the membrane-spanning domain of band 3 in intact cells causes global changes in membrane properties, including (i) displacement of a glycolytic enzyme complex from the membrane, (ii) inhibition of anion transport, and (iii) rupture of the band 3-ankyrin bridge connecting the spectrin-based cytoskeleton to the membrane...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27848995/a-novel-enu-induced-ankyrin-1-mutation-impairs-parasite-invasion-and-increases-erythrocyte-clearance-during-malaria-infection-in-mice
#15
Hong Ming Huang, Denis C Bauer, Patrick M Lelliott, Andreas Greth, Brendan J McMorran, Simon J Foote, Gaetan Burgio
Genetic defects in various red blood cell (RBC) cytoskeletal proteins have been long associated with changes in susceptibility towards malaria infection. In particular, while ankyrin (Ank-1) mutations account for approximately 50% of hereditary spherocytosis (HS) cases, an association with malaria is not well-established, and conflicting evidence has been reported. We describe a novel N-ethyl-N-nitrosourea (ENU)-induced ankyrin mutation MRI61689 that gives rise to two different ankyrin transcripts: one with an introduced splice acceptor site resulting a frameshift, the other with a skipped exon...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27832206/structural-functional-and-phylogenetic-analysis-of-sperm-lysozyme-like-proteins
#16
Shalini Kalra, Mangottil Ayyappan Pradeep, Ashok K Mohanty, Jai K Kaushik
Sperm lysozyme-like proteins belonging to c-type lysozyme family evolved in multiple forms. Lysozyme-like proteins, viz., LYZL2, LYZL3 or SLLP1, LYZL4, LYZL5 and LYZL6 are expressed in the testis of mammals. Not all members of LYZL family have been uniformly and unambiguously identified in the genome and proteome of mammals. Some studies suggested a role of SLLP1 and LYZL4 in fertilization; however, the function of other LYZL proteins is unknown. We identified all known forms of LYZL proteins in buffalo sperm by LC-MS/MS...
2016: PloS One
https://www.readbyqxmd.com/read/27827994/ibtk-differently-modulates-gene-expression-and-rna-splicing-in-hela-and-k562-cells
#17
Giuseppe Fiume, Annarita Scialdone, Francesca Rizzo, Maria Rosaria De Filippo, Carmelo Laudanna, Francesco Albano, Gaetanina Golino, Eleonora Vecchio, Marilena Pontoriero, Selena Mimmi, Simona Ceglia, Antonio Pisano, Enrico Iaccino, Camillo Palmieri, Sergio Paduano, Giuseppe Viglietto, Alessandro Weisz, Giuseppe Scala, Ileana Quinto
The IBTK gene encodes the major protein isoform IBTKα that was recently characterized as substrate receptor of Cul3-dependent E3 ligase, regulating ubiquitination coupled to proteasomal degradation of Pdcd4, an inhibitor of translation. Due to the presence of Ankyrin-BTB-RCC1 domains that mediate several protein-protein interactions, IBTKα could exert expanded regulatory roles, including interaction with transcription regulators. To verify the effects of IBTKα on gene expression, we analyzed HeLa and K562 cell transcriptomes by RNA-Sequencing before and after IBTK knock-down by shRNA transduction...
November 7, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27827953/blocking-trpa1-in-respiratory-disorders-does-it-hold-a-promise
#18
REVIEW
Indranil Mukhopadhyay, Abhay Kulkarni, Neelima Khairatkar-Joshi
Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel is expressed abundantly on the C fibers that innervate almost entire respiratory tract starting from oral cavity and oropharynx, conducting airways in the trachea, bronchi, terminal bronchioles, respiratory bronchioles and upto alveolar ducts and alveoli. Functional presence of TRPA1 on non-neuronal cells got recognized recently. TRPA1 plays a well-recognized role of "chemosensor", detecting presence of exogenous irritants and endogenous pro-inflammatory mediators that are implicated in airway inflammation and sensory symptoms like chronic cough, asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis and cystic fibrosis...
November 5, 2016: Pharmaceuticals
https://www.readbyqxmd.com/read/27826691/drd2-c957t-polymorphism-is-associated-with-improved-6-month-verbal-learning-following-traumatic-brain-injury
#19
John K Yue, Ethan A Winkler, Jonathan W Rick, John F Burke, Thomas W McAllister, Sam S Oh, Esteban G Burchard, Donglei Hu, Jonathan Rosand, Nancy R Temkin, Frederick K Korley, Marco D Sorani, Adam R Ferguson, Hester F Lingsma, Sourabh Sharma, Caitlin K Robinson, Esther L Yuh, Phiroz E Tarapore, Kevin K W Wang, Ava M Puccio, Pratik Mukherjee, Ramon Diaz-Arrastia, Wayne A Gordon, Alex B Valadka, David O Okonkwo, Geoffrey T Manley
Traumatic brain injury (TBI) often leads to heterogeneous clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism (SNP) in the dopamine D2 receptor (DRD2) may influence cognitive deficits following TBI. However, part of the association with DRD2 has been attributed to genetic variability within the adjacent ankyrin repeat and kinase domain containing 1 protein (ANKK1). Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether a novel DRD2 C957T polymorphism (rs6277) influences outcome on a cognitive battery at 6 months following TBI-California Verbal Learning Test (CVLT-II), Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), and Trail Making Test (TMT)...
November 8, 2016: Neurogenetics
https://www.readbyqxmd.com/read/27824920/the-outer-pore-and-selectivity-filter-of-trpa1
#20
Adam P Christensen, Nurunisa Akyuz, David P Corey
TRPA1 (transient-receptor-potential-related ion channel with ankyrin domains) is a direct receptor or indirect effector for a wide variety of nociceptive signals, and thus is a compelling target for development of analgesic pharmaceuticals such as channel blockers. Recently, the structure of TRPA1 was reported, providing insights into channel assembly and pore architecture. Here we report whole-cell and single-channel current recordings of wild-type human TRPA1 as well as TRPA1 bearing point mutations of key charged residues in the outer pore...
2016: PloS One
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