Common Low Complexity Regions for SARS-Cov-2 and Human
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Bioinformatics Analysis for the Identification of Differentially Expressed Genes and Related Signaling Pathways in H
Bioinformatics analysis for the identification of differentially expressed genes and related signaling pathways in H. pylori-CagA transfected gastric cancer cells Dingyu Chen*, Chao Li, Yan Zhao, Jianjiang Zhou, Qinrong Wang and Yuan Xie* Key Laboratory of Endemic and Ethnic Diseases , Ministry of Education, Guizhou Medical University, Guiyang, China * These authors contributed equally to this work. ABSTRACT Aim. Helicobacter pylori cytotoxin-associated protein A (CagA) is an important vir- ulence factor known to induce gastric cancer development. However, the cause and the underlying molecular events of CagA induction remain unclear. Here, we applied integrated bioinformatics to identify the key genes involved in the process of CagA- induced gastric epithelial cell inflammation and can ceration to comprehend the potential molecular mechanisms involved. Materials and Methods. AGS cells were transected with pcDNA3.1 and pcDNA3.1::CagA for 24 h. The transfected cells were subjected to transcriptome sequencing to obtain the expressed genes. Differentially expressed genes (DEG) with adjusted P value < 0.05, | logFC |> 2 were screened, and the R package was applied for gene ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The differential gene protein–protein interaction (PPI) network was constructed using the STRING Cytoscape application, which conducted visual analysis to create the key function networks and identify the key genes. Next, the Submitted 20 August 2020 Kaplan–Meier plotter survival analysis tool was employed to analyze the survival of the Accepted 11 March 2021 key genes derived from the PPI network. Further analysis of the key gene expressions Published 15 April 2021 in gastric cancer and normal tissues were performed based on The Cancer Genome Corresponding author Atlas (TCGA) database and RT-qPCR verification. -
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bioRxiv preprint doi: https://doi.org/10.1101/2020.09.02.279679; this version posted September 2, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. A high-throughput CRISPR interference screen for dissecting functional regulators of GPCR/cAMP signaling Khairunnisa Mentari Semesta1, Ruilin Tian2,3,4, Martin Kampmann2,3, Mark von Zastrow5,6 and Nikoleta G. Tsvetanova1* 1 Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA 2 Insitute for Neurodegenerative Diseases, Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA 3 Chen-Zuckerberg Biohub, San Francisco, CA 94158, USA 4 Biophysics Graduate Program, University of California, San Francisco, CA 94158, USA 5 Department of Psychiatry, University of California, San Francisco, CA 94158, USA 6 Department of Cellular & Molecular Pharmacology, University of California, San Francisco, CA 94158, USA * Correspondence: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.09.02.279679; this version posted September 2, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Abstract 2 G protein-coupled receptors (GPCRs) allow cells to respond to chemical and sensory 3 stimuli through generation of second messengers, such as cyclic AMP (cAMP), which in 4 turn mediate a myriad of processes, including cell survival, proliferation, and 5 differentiation. -
Nº Ref Uniprot Proteína Péptidos Identificados Por MS/MS 1 P01024
Document downloaded from http://www.elsevier.es, day 26/09/2021. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited. Nº Ref Uniprot Proteína Péptidos identificados 1 P01024 CO3_HUMAN Complement C3 OS=Homo sapiens GN=C3 PE=1 SV=2 por 162MS/MS 2 P02751 FINC_HUMAN Fibronectin OS=Homo sapiens GN=FN1 PE=1 SV=4 131 3 P01023 A2MG_HUMAN Alpha-2-macroglobulin OS=Homo sapiens GN=A2M PE=1 SV=3 128 4 P0C0L4 CO4A_HUMAN Complement C4-A OS=Homo sapiens GN=C4A PE=1 SV=1 95 5 P04275 VWF_HUMAN von Willebrand factor OS=Homo sapiens GN=VWF PE=1 SV=4 81 6 P02675 FIBB_HUMAN Fibrinogen beta chain OS=Homo sapiens GN=FGB PE=1 SV=2 78 7 P01031 CO5_HUMAN Complement C5 OS=Homo sapiens GN=C5 PE=1 SV=4 66 8 P02768 ALBU_HUMAN Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=2 66 9 P00450 CERU_HUMAN Ceruloplasmin OS=Homo sapiens GN=CP PE=1 SV=1 64 10 P02671 FIBA_HUMAN Fibrinogen alpha chain OS=Homo sapiens GN=FGA PE=1 SV=2 58 11 P08603 CFAH_HUMAN Complement factor H OS=Homo sapiens GN=CFH PE=1 SV=4 56 12 P02787 TRFE_HUMAN Serotransferrin OS=Homo sapiens GN=TF PE=1 SV=3 54 13 P00747 PLMN_HUMAN Plasminogen OS=Homo sapiens GN=PLG PE=1 SV=2 48 14 P02679 FIBG_HUMAN Fibrinogen gamma chain OS=Homo sapiens GN=FGG PE=1 SV=3 47 15 P01871 IGHM_HUMAN Ig mu chain C region OS=Homo sapiens GN=IGHM PE=1 SV=3 41 16 P04003 C4BPA_HUMAN C4b-binding protein alpha chain OS=Homo sapiens GN=C4BPA PE=1 SV=2 37 17 Q9Y6R7 FCGBP_HUMAN IgGFc-binding protein OS=Homo sapiens GN=FCGBP PE=1 SV=3 30 18 O43866 CD5L_HUMAN CD5 antigen-like OS=Homo -
Characterized by Array CGH in a Boy with Cat-Eye Syndrome Irén Haltrich1*, Henriett Pikó2, Eszter Kiss1, Zsuzsa Tóth1, Veronika Karcagi2 and György Fekete1
Haltrich et al. Molecular Cytogenetics 2014, 7:37 http://www.molecularcytogenetics.org/content/7/1/37 CASE REPORT Open Access A de novo atypical ring sSMC(22) characterized by array CGH in a boy with cat-eye syndrome Irén Haltrich1*, Henriett Pikó2, Eszter Kiss1, Zsuzsa Tóth1, Veronika Karcagi2 and György Fekete1 Abstract Background: Microduplications 22q11 have been characterized as a genomic duplication syndrome mediated by nonallelic homologous recombination between region-specific low-copy repeats. Here we report on a 19 years old boy with intellectual disability having an unexpected structurally complex ring small supernumerary marker chromosome (sSMC) originated from a larger trisomy and a smaller tetrasomy of proximal 22q11 harboring additional copies of cat eye syndrome critical regions genes. Results: Principal clinical features were: anorectal and urogenital malformations, total anomalous pulmonary venous return with secundum ASD, hearing defect, preauricular pits, seizure and eczema. The proband also presented some rare or so far not reported clinical findings such as hyperinsulinaemia, severe immunodeficiency and grave cognitive deficits. Chromosome analysis revealed a mosaic karyotype with the presence of a small ring-like marker in 60% of cells. Array CGH detected approximately an 1,2 Mb single and a 0,2 Mb double copy gain of the proximal long arm of chromosome 22. The 1,3 Mb intervening region of chromosome 22 from centromere to the breakpoints showed no copy alteration. The karyotype of the patient was defined as 47,XY,+mar[60]/46,XY[40].ish idic r(22)(q11.1.q11.21) × 4.arr 22q11(17,435, 645-18,656,678) × 3,(17,598,642-17,799,783) × 4 dn. -
Alternatively Spliced Homologous Exons Have Ancient Origins and Are Highly Expressed at the Protein Level
RESEARCH ARTICLE Alternatively Spliced Homologous Exons Have Ancient Origins and Are Highly Expressed at the Protein Level Federico Abascal1, Iakes Ezkurdia2, Juan Rodriguez-Rivas1, Jose Manuel Rodriguez3, Angela del Pozo4, Jesús Vázquez5, Alfonso Valencia1,3*, Michael L. Tress1* 1 Structural Biology and Bioinformatics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain, 2 Unidad de Proteómica, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain, 3 National Bioinformatics Institute (INB), Spanish National Cancer Research Centre (CNIO), Madrid, Spain, 4 Instituto de Genetica Medica y Molecular, Hospital Universitario La Paz, Madrid, Spain, 5 Laboratorio de Proteómica Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares (CNIC) Madrid, Spain * [email protected] (AV); [email protected] (MLT) OPEN ACCESS Abstract Citation: Abascal F, Ezkurdia I, Rodriguez-Rivas J, Alternative splicing of messenger RNA can generate a wide variety of mature RNA tran- Rodriguez JM, del Pozo A, Vázquez J, et al. (2015) Alternatively Spliced Homologous Exons Have scripts, and these transcripts may produce protein isoforms with diverse cellular functions. Ancient Origins and Are Highly Expressed at the While there is much supporting evidence for the expression of alternative transcripts, the Protein Level. PLoS Comput Biol 11(6): e1004325. same is not true for the alternatively spliced protein products. Large-scale mass spectrosco- doi:10.1371/journal.pcbi.1004325 py experiments have identified evidence of alternative splicing at the protein level, but with Editor: Lukas Käll, Royal Institute of Technology, conflicting results. Here we carried out a rigorous analysis of the peptide evidence from SWEDEN eight large-scale proteomics experiments to assess the scale of alternative splicing that is Received: December 16, 2014 detectable by high-resolution mass spectroscopy. -
Chromosome 22Q11.2 Deletion Syndrome Associated with Congenital Heart Defects
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Taiwanese Journal of Obstetrics & Gynecology 53 (2014) 248e251 Contents lists available at ScienceDirect Taiwanese Journal of Obstetrics & Gynecology journal homepage: www.tjog-online.com Case Report Prenatal diagnosis and molecular cytogenetic characterization of chromosome 22q11.2 deletion syndrome associated with congenital heart defects Yu-Ling Kuo a, Chih-Ping Chen b, c, d, e, f, g, *, Liang-Kai Wang b, Tsang-Ming Ko h, Tung-Yao Chang i, Schu-Rern Chern c, Peih-Shan Wu j, Yu-Ting Chen c, Shu-Yuan Chang b a Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan b Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan c Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan d Department of Biotechnology, Asia University, Taichung, Taiwan e School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan f Institute of Clinical and Community Health Nursing, National Yang-Ming University, Taipei, Taiwan g Department of Obstetrics and Gynecology, School of Medicine, National Yang-Ming University, Taipei, Taiwan h GenePhile Bioscience Laboratory, Ko's Obstetrics and Gynecology, Taipei, Taiwan i Taiji Fetal Medicine Center, Taipei, Taiwan j Gene Biodesign Co. Ltd, Taipei, Taiwan article info abstract Article history: Objective: To report prenatal diagnosis of 22q11.2 deletion syndrome in a pregnancy with congenital Accepted 16 April 2014 heart defects in the fetus. Case report: A 26-year-old, primigravid woman was referred for counseling at 24 weeks of gestation Keywords: because of abnormal ultrasound findings of fetal congenital heart defects. -
Sheep Genome Functional Annotation Reveals Proximal Regulatory Elements Contributed to the Evolution of Modern Breeds
ARTICLE DOI: 10.1038/s41467-017-02809-1 OPEN Sheep genome functional annotation reveals proximal regulatory elements contributed to the evolution of modern breeds Marina Naval-Sanchez1, Quan Nguyen1, Sean McWilliam1, Laercio R. Porto-Neto1, Ross Tellam1, Tony Vuocolo1, Antonio Reverter1, Miguel Perez-Enciso 2,3, Rudiger Brauning4, Shannon Clarke4, Alan McCulloch4, Wahid Zamani5, Saeid Naderi 6, Hamid Reza Rezaei7, Francois Pompanon 8, Pierre Taberlet8, Kim C. Worley9, Richard A. Gibbs9, Donna M. Muzny9, Shalini N. Jhangiani9, Noelle Cockett10, Hans Daetwyler11,12 & James Kijas1 1234567890():,; Domestication fundamentally reshaped animal morphology, physiology and behaviour, offering the opportunity to investigate the molecular processes driving evolutionary change. Here we assess sheep domestication and artificial selection by comparing genome sequence from 43 modern breeds (Ovis aries) and their Asian mouflon ancestor (O. orientalis)to identify selection sweeps. Next, we provide a comparative functional annotation of the sheep genome, validated using experimental ChIP-Seq of sheep tissue. Using these annotations, we evaluate the impact of selection and domestication on regulatory sequences and find that sweeps are significantly enriched for protein coding genes, proximal regulatory elements of genes and genome features associated with active transcription. Finally, we find individual sites displaying strong allele frequency divergence are enriched for the same regulatory features. Our data demonstrate that remodelling of gene expression is likely to have been one of the evolutionary forces that drove phenotypic diversification of this common livestock species. 1 CSIRO Agriculture and Food, 306 Carmody Road, St. Lucia 4067 QLD, Australia. 2 Centre for Research in Agricultural Genomics (CRAG), Bellaterra 08193, Spain. 3 ICREA, Carrer de Lluís Companys 23, Barcelona 08010, Spain. -
Agricultural University of Athens
ΓΕΩΠΟΝΙΚΟ ΠΑΝΕΠΙΣΤΗΜΙΟ ΑΘΗΝΩΝ ΣΧΟΛΗ ΕΠΙΣΤΗΜΩΝ ΤΩΝ ΖΩΩΝ ΤΜΗΜΑ ΕΠΙΣΤΗΜΗΣ ΖΩΙΚΗΣ ΠΑΡΑΓΩΓΗΣ ΕΡΓΑΣΤΗΡΙΟ ΓΕΝΙΚΗΣ ΚΑΙ ΕΙΔΙΚΗΣ ΖΩΟΤΕΧΝΙΑΣ ΔΙΔΑΚΤΟΡΙΚΗ ΔΙΑΤΡΙΒΗ Εντοπισμός γονιδιωματικών περιοχών και δικτύων γονιδίων που επηρεάζουν παραγωγικές και αναπαραγωγικές ιδιότητες σε πληθυσμούς κρεοπαραγωγικών ορνιθίων ΕΙΡΗΝΗ Κ. ΤΑΡΣΑΝΗ ΕΠΙΒΛΕΠΩΝ ΚΑΘΗΓΗΤΗΣ: ΑΝΤΩΝΙΟΣ ΚΟΜΙΝΑΚΗΣ ΑΘΗΝΑ 2020 ΔΙΔΑΚΤΟΡΙΚΗ ΔΙΑΤΡΙΒΗ Εντοπισμός γονιδιωματικών περιοχών και δικτύων γονιδίων που επηρεάζουν παραγωγικές και αναπαραγωγικές ιδιότητες σε πληθυσμούς κρεοπαραγωγικών ορνιθίων Genome-wide association analysis and gene network analysis for (re)production traits in commercial broilers ΕΙΡΗΝΗ Κ. ΤΑΡΣΑΝΗ ΕΠΙΒΛΕΠΩΝ ΚΑΘΗΓΗΤΗΣ: ΑΝΤΩΝΙΟΣ ΚΟΜΙΝΑΚΗΣ Τριμελής Επιτροπή: Aντώνιος Κομινάκης (Αν. Καθ. ΓΠΑ) Ανδρέας Κράνης (Eρευν. B, Παν. Εδιμβούργου) Αριάδνη Χάγερ (Επ. Καθ. ΓΠΑ) Επταμελής εξεταστική επιτροπή: Aντώνιος Κομινάκης (Αν. Καθ. ΓΠΑ) Ανδρέας Κράνης (Eρευν. B, Παν. Εδιμβούργου) Αριάδνη Χάγερ (Επ. Καθ. ΓΠΑ) Πηνελόπη Μπεμπέλη (Καθ. ΓΠΑ) Δημήτριος Βλαχάκης (Επ. Καθ. ΓΠΑ) Ευάγγελος Ζωίδης (Επ.Καθ. ΓΠΑ) Γεώργιος Θεοδώρου (Επ.Καθ. ΓΠΑ) 2 Εντοπισμός γονιδιωματικών περιοχών και δικτύων γονιδίων που επηρεάζουν παραγωγικές και αναπαραγωγικές ιδιότητες σε πληθυσμούς κρεοπαραγωγικών ορνιθίων Περίληψη Σκοπός της παρούσας διδακτορικής διατριβής ήταν ο εντοπισμός γενετικών δεικτών και υποψηφίων γονιδίων που εμπλέκονται στο γενετικό έλεγχο δύο τυπικών πολυγονιδιακών ιδιοτήτων σε κρεοπαραγωγικά ορνίθια. Μία ιδιότητα σχετίζεται με την ανάπτυξη (σωματικό βάρος στις 35 ημέρες, ΣΒ) και η άλλη με την αναπαραγωγική -
Actin Mutations and Their Role in Disease
International Journal of Molecular Sciences Review Actin Mutations and Their Role in Disease Francine Parker, Thomas G. Baboolal and Michelle Peckham * School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK; [email protected] (F.P.); [email protected] (T.G.B.) * Correspondence: [email protected]; Tel.: +44-(0)1133-434348 Received: 25 March 2020; Accepted: 7 May 2020; Published: 10 May 2020 Abstract: Actin is a widely expressed protein found in almost all eukaryotic cells. In humans, there are six different genes, which encode specific actin isoforms. Disease-causing mutations have been described for each of these, most of which are missense. Analysis of the position of the resulting mutated residues in the protein reveals mutational hotspots. Many of these occur in regions important for actin polymerization. We briefly discuss the challenges in characterizing the effects of these actin mutations, with a focus on cardiac actin mutations. Keywords: actin; mutation; polymerization; myosin 1. Introduction Actin is a globular protein (G-actin) that assembles into filaments (F-actin) and is important for cell movement, intracellular movement, muscle contraction and many other functions. There are six actin genes in the human genome. Three of these encode the α-actin isoforms found in cardiac, skeletal or smooth muscle (ACTC1, ACTA1 and ACTA2, respectively). Two encode γ-actin, of which one is widely expressed (ACTG1) and the other is smooth muscle specific (ACTG2). The final gene encodes the widely expressed β-actin (ACTB). These actin isoforms are highly (>90%) conserved at the protein level. Actin is a promiscuous protein, interacting with many other proteins [1], and is also subject to many different post-translational modifications [2]. -
Transcriptomics Uncovers Substantial Variability Associated with Alterations in Manufacturing Processes of Macrophage Cell Therapy Products Olga L
www.nature.com/scientificreports OPEN Transcriptomics uncovers substantial variability associated with alterations in manufacturing processes of macrophage cell therapy products Olga L. Gurvich1,3, Katja A. Puttonen1,3, Aubrey Bailey1, Anssi Kailaanmäki1, Vita Skirdenko1, Minna Sivonen1, Sanna Pietikäinen1, Nigel R. Parker2, Seppo Ylä‑Herttuala2 & Tuija Kekarainen1* Gene expression plasticity is central for macrophages’ timely responses to cues from the microenvironment permitting phenotypic adaptation from pro‑infammatory (M1) to wound healing and tissue‑regenerative (M2, with several subclasses). Regulatory macrophages are a distinct macrophage type, possessing immunoregulatory, anti‑infammatory, and angiogenic properties. Due to these features, regulatory macrophages are considered as a potential cell therapy product to treat clinical conditions, e.g., non‑healing diabetic foot ulcers. In this study we characterized two diferently manufactured clinically relevant regulatory macrophages, programmable cells of monocytic origin and comparator macrophages (M1, M2a and M0) using fow‑cytometry, RT‑qPCR, phagocytosis and secretome measurements, and RNA‑Seq. We demonstrate that conventional phenotyping had a limited potential to discriminate diferent types of macrophages which was ameliorated when global transcriptome characterization by RNA‑Seq was employed. Using this approach we confrmed that macrophage manufacturing processes can result in a highly reproducible cell phenotype. At the same time, minor changes introduced in manufacturing -
Identification of Novel Regulatory Genes in Acetaminophen
IDENTIFICATION OF NOVEL REGULATORY GENES IN ACETAMINOPHEN INDUCED HEPATOCYTE TOXICITY BY A GENOME-WIDE CRISPR/CAS9 SCREEN A THESIS IN Cell Biology and Biophysics and Bioinformatics Presented to the Faculty of the University of Missouri-Kansas City in partial fulfillment of the requirements for the degree DOCTOR OF PHILOSOPHY By KATHERINE ANNE SHORTT B.S, Indiana University, Bloomington, 2011 M.S, University of Missouri, Kansas City, 2014 Kansas City, Missouri 2018 © 2018 Katherine Shortt All Rights Reserved IDENTIFICATION OF NOVEL REGULATORY GENES IN ACETAMINOPHEN INDUCED HEPATOCYTE TOXICITY BY A GENOME-WIDE CRISPR/CAS9 SCREEN Katherine Anne Shortt, Candidate for the Doctor of Philosophy degree, University of Missouri-Kansas City, 2018 ABSTRACT Acetaminophen (APAP) is a commonly used analgesic responsible for over 56,000 overdose-related emergency room visits annually. A long asymptomatic period and limited treatment options result in a high rate of liver failure, generally resulting in either organ transplant or mortality. The underlying molecular mechanisms of injury are not well understood and effective therapy is limited. Identification of previously unknown genetic risk factors would provide new mechanistic insights and new therapeutic targets for APAP induced hepatocyte toxicity or liver injury. This study used a genome-wide CRISPR/Cas9 screen to evaluate genes that are protective against or cause susceptibility to APAP-induced liver injury. HuH7 human hepatocellular carcinoma cells containing CRISPR/Cas9 gene knockouts were treated with 15mM APAP for 30 minutes to 4 days. A gene expression profile was developed based on the 1) top screening hits, 2) overlap with gene expression data of APAP overdosed human patients, and 3) biological interpretation including assessment of known and suspected iii APAP-associated genes and their therapeutic potential, predicted affected biological pathways, and functionally validated candidate genes. -
Mapping Axon Initial Segment Structure and Function by Multiplexed Proximity Biotinylation
ARTICLE https://doi.org/10.1038/s41467-019-13658-5 OPEN Mapping axon initial segment structure and function by multiplexed proximity biotinylation Hamdan Hamdan1,5, Brian C. Lim 1, Tomohiro Torii 1, Abhijeet Joshi1, Matthias Konning1, Cameron Smith 1, Donna J. Palmer2, Philip Ng2, Christophe Leterrier 3, Juan A. Oses-Prieto 4, Alma L. Burlingame4 & Matthew N. Rasband 1* Axon initial segments (AISs) generate action potentials and regulate the polarized distribu- tion of proteins, lipids, and organelles in neurons. While the mechanisms of AIS Na+ and K+ channel clustering are understood, the molecular mechanisms that stabilize the AIS and control neuronal polarity remain obscure. Here, we use proximity biotinylation and mass spectrometry to identify the AIS proteome. We target the biotin-ligase BirA* to the AIS by generating fusion proteins of BirA* with NF186, Ndel1, and Trim46; these chimeras map the molecular organization of AIS intracellular membrane, cytosolic, and microtubule compart- ments. Our experiments reveal a diverse set of biotinylated proteins not previously reported at the AIS. We show many are located at the AIS, interact with known AIS proteins, and their loss disrupts AIS structure and function. Our results provide conceptual insights and a resource for AIS molecular organization, the mechanisms of AIS stability, and polarized trafficking in neurons. 1 Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA. 2 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. 3 Aix-Marseille Univ, CNRS, INP, NeuroCyto, Marseille, France. 4 Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA. 5Present address: Department of Physiology, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia.