DOCSLIB.ORG

The Prion Protein Is Embedded in a Molecular Environment That Modulates Transforming Growth Factor Β and Integrin Signaling

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Prion Protein Is Embedded in a Molecular Environment That Modulates Transforming Growth Factor Β and Integrin Signaling The Prion Protein is Embedded in a Molecular Environment that Modulates Transforming Growth Factor β and Integrin Signaling by Farinaz Ghodrati A thesis submitted in conformity with the requirements for the degree of Master of Science Department of Laboratory Medicine and Pathobiology University of Toronto © Copyright by Farinaz Ghodrati 2018 The Prion Protein is Embedded in a Molecular Environment that Modulates Transforming Growth Factor β and Integrin Signaling Farinaz Ghodrati Master of Science Department of Laboratory Medicine and Pathobiology University of Toronto 2018 Abstract The prion protein (PrP) is known for its fundamental role in a group of neurodegenerative disorders, aptly called prion diseases. The function of the normal cellular prion protein (PrPC) as well as the underlying molecular mechanisms that lead to neurotoxicity in disease are still unresolved. The previously discovered evolutionary relationship between PrP and ZIP zinc transporters implicated PrPC in morphogenetic reprogramming events but also uncovered surprising differences when comparing signaling pathways downstream of PrPC in separate cellular paradigms. To extend this line of research, we combined CRISPR-Cas9-based genetic engineering to generate four relevant murine PrP-deficient cell models, with quantitative mass spectrometry-based analyses to compare the molecular environment of PrP in these models. Interestingly, a unified theme emerged from these studies that placed PrPC in a specialized membrane domain that modulates TGF beta and integrin signaling. ii Acknowledgments First and foremost, I would like to wholeheartedly thank my supervisor, Dr. Gerold Schmitt-Ulms for his exceptional mentorship and unwavering support throughout my studies. I credit his genuine passion and dedication to research and his keen scientific mind with helping me grow both personally and professionally over these last two years. Though my time under his mentorship has now ended, I will take the lessons I’ve learned here with me onwards through my career. I would also like to extend my thanks to the members of my advisory committee – Dr. Joel Watts and Dr. Sunit Das. Their advice and guidance have helped me immensely in my research. Additionally, many thanks to the tireless efforts of the Department of Laboratory Medicine and Pathobiology’s Graduate Coordinator, Dr. Harry P. Elsholtz, and the Graduate Administrator, Rama Ponda. I am also tremendously grateful for the pleasure and privilege of collaborating with past and present members of the Schmitt-Ulms lab – Dr. Hansen Wang, Louisa Wang, and Michael Solarski. My time here would not have been as productive or enjoyable without them. Special thanks to Dr. Declan Williams, who helped move this project leaps and bounds with his invaluable guidance and expertise in the field of mass spectrometry. And finally, this entire project would not have been possible without the accomplishments of Dr. Mohadeseh Mehrabian. To her, I express my immense gratitude for her untiring mentorship, guidance and, above all, friendship. Lastly, I would like to thank my friends and family for their love, patience, and support over the years, specifically, AS, NS, NR, NM and ABZ, for your unique sense of humour. I would also want to express my thanks to the colleagues at the Tanz CRND who provided me with tremendous scientific and personal support during my degree. And above all, my utmost appreciation to my parents for being such amazing sources of strength and support. iii Table of Contents Acknowledgments .................................................................................................................. iii Table of Contents ................................................................................................................... iv List of Tables ......................................................................................................................... vii List of Figures ....................................................................................................................... viii List of Appendices .................................................................................................................. ix Abbreviations .......................................................................................................................... x Chapter 1 ............................................................................................................................... 1 The Prion Protein: What We Do and Don’t Know ............................................................ 1 1.1 Introduction ......................................................................................................................... 1 1.2 Prion diseases ...................................................................................................................... 1 1.2.1 Overview of prion diseases ..................................................................................................... 1 1.2.2 Inherited human prion diseases ............................................................................................. 2 1.2.3 Acquired human prion diseases ............................................................................................. 3 1.2.4 Sporadic human prion diseases .............................................................................................. 5 1.3 Prion propagation ................................................................................................................ 7 1.3.1 How the prion concept came to be ........................................................................................ 7 1.3.2 PrPC expression is essential for prion infection ....................................................................... 8 1.3.3 Prion toxicity ........................................................................................................................... 9 1.4 Structure of the prion protein ............................................................................................ 10 1.4.1 Overview of the structural features of PrP ........................................................................... 10 1.4.2 Proteolytic processing of PrP ................................................................................................ 11 1.5 Evolutionary origin of the prion protein ............................................................................. 12 1.5.1 Discovery of the PrP-ZIP connection .................................................................................... 12 1.5.2 How PrP evolved from ZIP ancestors .................................................................................... 13 1.5.3 Further proof on the family reunion of PrP and ZIPs ............................................................ 14 1.6 Proposed functions of the prion protein ............................................................................. 15 1.6.1 Overview of the roles ascribed to PrPC ................................................................................. 15 1.6.2 Epithelial-to-mesenchymal transition .................................................................................. 16 1.6.3 Additional PrP-related phenotypes ...................................................................................... 17 iv 1.7 Methodology background .................................................................................................. 18 1.7.1 Overview of the experimental workflow .............................................................................. 18 1.7.2 Cell models ........................................................................................................................... 19 1.7.3 CRISPR-Cas9 knockout technology ....................................................................................... 20 1.7.4 Affinity capture matrix .......................................................................................................... 22 1.7.5 Mass spectrometry ............................................................................................................... 22 Chapter 2 .............................................................................................................................. 25 Rationale, Hypothesis and Objectives ............................................................................ 25 2.1 Rationale for the ZIP study ................................................................................................. 25 2.2 Rationale for the PrP interactome study ............................................................................ 26 Chapter 3 .............................................................................................................................. 28 ZIP6-mediated NCAM1 Phosphorylation ........................................................................ 28 3.1 Introduction ....................................................................................................................... 29 3.2 Results ............................................................................................................................... 30 3.2.1 In vitro phosphorylation of the longest NCAM1 isoform by GSK3B ..................................... 30 3.3 Discussion .......................................................................................................................... 32 3.4 Methods ...........................................................................................................................
Load more

Recommended publications
  • Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse
    Welcome to More Choice CD Marker Handbook For more information, please visit: Human bdbiosciences.com/eu/go/humancdmarkers Mouse bdbiosciences.com/eu/go/mousecdmarkers Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse CD3 CD3 CD (cluster of differentiation) molecules are cell surface markers T Cell CD4 CD4 useful for the identification and characterization of leukocytes. The CD CD8 CD8 nomenclature was developed and is maintained through the HLDA (Human Leukocyte Differentiation Antigens) workshop started in 1982. CD45R/B220 CD19 CD19 The goal is to provide standardization of monoclonal antibodies to B Cell CD20 CD22 (B cell activation marker) human antigens across laboratories. To characterize or “workshop” the antibodies, multiple laboratories carry out blind analyses of antibodies. These results independently validate antibody specificity. CD11c CD11c Dendritic Cell CD123 CD123 While the CD nomenclature has been developed for use with human antigens, it is applied to corresponding mouse antigens as well as antigens from other species. However, the mouse and other species NK Cell CD56 CD335 (NKp46) antibodies are not tested by HLDA. Human CD markers were reviewed by the HLDA. New CD markers Stem Cell/ CD34 CD34 were established at the HLDA9 meeting held in Barcelona in 2010. For Precursor hematopoetic stem cell only hematopoetic stem cell only additional information and CD markers please visit www.hcdm.org. Macrophage/ CD14 CD11b/ Mac-1 Monocyte CD33 Ly-71 (F4/80) CD66b Granulocyte CD66b Gr-1/Ly6G Ly6C CD41 CD41 CD61 (Integrin b3) CD61 Platelet CD9 CD62 CD62P (activated platelets) CD235a CD235a Erythrocyte Ter-119 CD146 MECA-32 CD106 CD146 Endothelial Cell CD31 CD62E (activated endothelial cells) Epithelial Cell CD236 CD326 (EPCAM1) For Research Use Only.
    [Show full text]
  • A Shared Pathway of Exosome Biogenesis Operates at Plasma And
    bioRxiv preprint doi: https://doi.org/10.1101/545228; this version posted February 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. A shared pathway of exosome biogenesis operates at plasma and endosome membranes Francis K. Fordjour1, George G. Daaboul2, and Stephen J. Gould1* 1Department of Biological Chemistry Johns Hopkins University Baltimore, MD USA 2Nanoview Biosciences Boston, MA USA Corresponding author: Stephen J. Gould, Ph.D. Department of Biological Chemistry Johns Hopkins University Baltimore, MD USA Email: [email protected] Tel (01) 443 847 9918 1 bioRxiv preprint doi: https://doi.org/10.1101/545228; this version posted February 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Summary: This study of exosome cargo protein budding reveals that cells use a common pathway for budding exosomes from plasma and endosome membranes, providing a new mechanistic explanation for exosome heterogeneity and a rational roadmap for exosome engineering. Keywords: Protein budding, tetraspanin, endosome, plasma membrane, extracellular vesicle, CD9, CD63, CD81, SPIR, interferometry Abbreviations: EV, extracellular vesicles; IB, immunoblot; IFM, immunofluorescence microscopy; IPMC, intracellular plasma membrane-connected compartment; MVB, multivesicular body; SPIR, single-particle interferometric reflectance; SPIRI, single-particle interferometric reflectance imaging 2 bioRxiv preprint doi: https://doi.org/10.1101/545228; this version posted February 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved.
    [Show full text]
  • Activation of Epithelial CD98 Glycoprotein Perpetuates Colonic Inflammation
    Laboratory Investigation (2005) 85, 932–941 & 2005 USCAP, Inc All rights reserved 0023-6837/05 $30.00 www.laboratoryinvestigation.org Activation of epithelial CD98 glycoprotein perpetuates colonic inflammation Torsten Kucharzik1, Andreas Lugering1, Yutao Yan2, Adel Driss2, Laetitia Charrier2, Shanthi Sitaraman2 and Didier Merlin2 1Department of Medicine B, Mu¨nster University of Mu¨nster, Germany and 2Department of Medicine, Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA, USA Anomalies in the regulation and function of integrins have been implicated in the etiology of various pathologic conditions, including inflammatory disorders such as irritable bowel disease. Several classes of cell surface glycoproteins such as CD98 have been shown to play roles in integrins-mediated events. Here, we investigated the role of CD98 in intestinal inflammation using both in vivo and in vitro approaches. We found that in Caco2- BBE monolayers and colonic tissues, expression of CD98 was upregulated by the proinflammatory cytokine, interferon gamma (INF c). Furthermore, CD98 was highly upregulated in colonic tissues from mice with active colitis induced by dextran sodium sulfate (DSS), but not in DSS-treated INF c À/À mice. Administration of an anti-CD98 antibody worsened DSS-induced colitis in mice but had no effect on untreated control mice. Finally, we used Caco2-BBE cell monolayers to model intestinal epithelial wound healing, and found that activation of epithelial CD98 in DSS-treated monolayers inhibited monolayer reconstitution, but had no affect on untreated control monolayers. Our data collectively indicate that (i) CD98 upregulation is mediated by INF c during intestinal inflammation and (ii) activation of epithelial CD98 protein aggravates intestinal inflammation by reducing intestinal epithelial reconstitution.
    [Show full text]
  • CD98 [19] Among Others [5][23]
    bioRxiv preprint doi: https://doi.org/10.1101/2021.04.15.439921; this version posted April 18, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Physiological Substrates and Ontogeny-Specific Expression of the Ubiquitin Ligases 2 MARCH1 and MARCH8 3 4 Patrick Schriek1, Haiyin Liu1, Alan C. Ching1, Pauline Huang1, Nishma Gupta1, Kayla R. 5 Wilson1, MinHsuang Tsai1, Yuting Yan2, Christophe F. Macri1, Laura F. Dagley3,4, Giuseppe 6 Infusini3,4, Andrew I. Webb3,4, Hamish McWilliam1,2, Satoshi Ishido5, Justine D. Mintern1 and 7 Jose A. Villadangos1,2 8 9 1Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology 10 Institute, The University of Melbourne, Parkville, VIC 3010, Australia. 11 2Department of Microbiology and Immunology, Peter Doherty Institute for Infection and 12 Immunity, The University of Melbourne, Parkville, VIC 3010, Australia. 13 3Advanced Technology and Biology Division, The Walter and Eliza Hall Institute of Medical 14 Research, Parkville, VIC 3052, Australia. 15 4Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. 16 5Department of Microbiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 17 17 663-8501, Japan 18 19 20 21 Correspondence to Justine D. Mintern ([email protected]) or 22 Jose A. Villadangos ([email protected]) 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.04.15.439921; this version posted April 18, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder.
    [Show full text]
  • Identification of Anti-CD98 Antibody Mimotopes for Inducing Antibodies with Antitumor Activity by Mimotope Immunization
    Identification of anti-CD98 antibody mimotopes for inducing antibodies with antitumor activity by mimotope immunization Misa Saito,1,3 Masahiro Kondo,1,3 Motohiro Ohshima,1 Kazuki Deguchi,1 Hideki Hayashi,1 Kazuyuki Inoue,1 Daiki Tsuji,1 Takashi Masuko2 and Kunihiko Itoh1 1Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka; 2Laboratory of Cell Biology, School of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Japan Key words A mimotope is an antibody-epitope-mimicking peptide retrieved from a phage CD98, mimotope, monoclonal antibody, phage display, display random peptide library. Immunization with antitumor antibody-derived recombinant Fab mimotopes is promising for inducing antitumor immunity in hosts. In this study, Correspondence we isolated linear and constrained mimotopes from HBJ127, a tumor-suppressing Kunihiko Itoh, Clinical Pharmacology and Genetics, anti-CD98 heavy chain mAb, and determined their abilities for induction of anti- School of Pharmaceutical Sciences, University of Shizuoka, tumor activity equal to that of the parent antibody. We detected elevated levels 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. of antipeptide responses, but failed to detect reactivity against native CD98- Tel/Fax: +81-54-264-5673; expressing HeLa cells in sera of immunized mice. Phage display panning and E-mail: [email protected] selection of mimotope-immunized mouse spleen-derived antibody Fab library 3These authors contributed equally to this work. showed that HeLa cell-reactive Fabs were successfully retrieved from the library. This finding indicates that native antigen-reactive Fab clones represented an Funding information undetectable minor population in mimotope-induced antibody repertoire.
    [Show full text]
  • Recent Advances in Orally Administered Cell-Specific Nanotherapeutics for Inflammatory Bowel Disease
    Submit a Manuscript: http://www.wjgnet.com/esps/ World J Gastroenterol 2016 September 14; 22(34): 7718-7726 Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx ISSN 1007-9327 (print) ISSN 2219-2840 (online) DOI: 10.3748/wjg.v22.i34.7718 © 2016 Baishideng Publishing Group Inc. All rights reserved. REVIEW Recent advances in orally administered cell-specific nanotherapeutics for inflammatory bowel disease Xiao-Ying Si, Didier Merlin, Bo Xiao Xiao-Ying Si, Bo Xiao, Institute for Clean Energy and Advanced Received: March 21, 2016 Materials, Faculty of Materials and Energy, Southwest University, Peer-review started: March 22, 2016 Chongqing 400715, China First decision: May 12, 2016 Revised: July 11, 2016 Didier Merlin, Bo Xiao, Institute for Biomedical Sciences, Accepted: July 31, 2016 Center for Diagnostics and Therapeutics, Georgia State Article in press: August 1, 2016 University, Atlanta, GA 30302, United States Published online: September 14, 2016 Didier Merlin, Atlanta Veterans Affairs Medical Center, Decatur, GA 30033, United States Author contributions: All authors contributed equally to this Abstract work. Inflammatory bowel disease (IBD) is a chronic relapsing disease in gastrointestinal tract. Conventional Supported by the National Natural Science Foundation of China, medications lack the efficacy to offer complete No. 51503172 and No. 81571807; the Fundamental Research remission in IBD therapy, and usually associate with Funds for the Central Universities, No. SWU114086 and No. serious side effects. Recent studies indicated that XDJK2015C067; and the Scientific Research Foundation for the nanoparticle-based nanotherapeutics may offer precise Returned Overseas Chinese Scholars (State Education Ministry), and safe alternative to conventional medications via the Department of Veterans Affairs (Merit Award to Merlin D); enhanced targeting, sustained drug release, and the National Institutes of Health of Diabetes and Digestive and decreased adverse effects.
    [Show full text]
  • Genetic Disruption of the Multifunctional CD98/LAT1 Complex Demonstrates the Key Role of Essential Amino Acid Transport in the Control of Mtorc1 and Tumor Growth
    Published OnlineFirst June 14, 2016; DOI: 10.1158/0008-5472.CAN-15-3376 Cancer Therapeutics, Targets, and Chemical Biology Research Genetic Disruption of the Multifunctional CD98/ LAT1 Complex Demonstrates the Key Role of Essential Amino Acid Transport in the Control of mTORC1 and Tumor Growth Yann Cormerais1, Sandy Giuliano2, Renaud LeFloch2, Beno^t Front1, Jerome Durivault1, Eric Tambutte3, Pierre-Andre Massard1, Laura Rodriguez de la Ballina4, Hitoshi Endou5, Michael F. Wempe6, Manuel Palacin4, Scott K. Parks1, and Jacques Pouyssegur1,2 Abstract The CD98/LAT1 complex is overexpressed in aggressive human inhibition, and severe in vitro and in vivo tumor growth arrest. We cancers and is thereby described as a potential therapeutic target. show that this severe growth phenotype is independent of the This complex promotes tumorigenesis with CD98 (4F2hc) engag- level of expression of CD98 in the six tumor cell lines. Surpris- ing b-integrin signaling while LAT1 (SLC7A5) imports essential ingly, CD98KO cells with only 10% EAA transport activity dis- amino acids (EAA) and promotes mTORC1 activity. However, it is played a normal growth phenotype, with mTORC1 activity and unclear as to which member of the heterodimer carries the most tumor growth rate undistinguishable from wild-type cells. How- prevalent protumoral action. To answer this question, we ever, CD98KO cells became extremely sensitive to inhibition or explored the tumoral potential of each member by gene disrup- genetic disruption of LAT1 (CD98KO/LAT1KO). This finding tion of CD98, LAT1, or both and by inhibition of LAT1 with the demonstrates that the tumoral potential of CD98KO cells is due selective inhibitor (JPH203) in six human cancer cell lines from to residual LAT1 transport activity.
    [Show full text]
  • Retinoid X Receptor Agonists Increase Bcl2a1 Expression and Decrease Apoptosis of Naive T Lymphocytes1
    The Journal of Immunology Retinoid X Receptor Agonists Increase Bcl2a1 Expression and Decrease Apoptosis of Naive T Lymphocytes1 Reuven Rasooly,* Gertrud U. Schuster,* Jeffrey P. Gregg,† Jia-Hao Xiao,‡ Roshantha A. S. Chandraratna,‡ and Charles B. Stephensen2* Vitamin A affects many aspects of T lymphocyte development and function. The vitamin A metabolites all-trans- and 9-cis-retinoic acid regulate gene expression by binding to the retinoic acid receptor (RAR), while 9-cis-retinoic acid also binds to the retinoid X receptor (RXR). Naive DO11.10 T lymphocytes expressed mRNA and protein for RAR-␣, RXR-␣, and RXR-␤. DNA microar- ray analysis was used to identify RXR-responsive genes in naive DO11.10 T lymphocytes treated with the RXR agonist AGN194204. A total of 128 genes was differentially expressed, including 16 (15%) involved in cell growth or apoptosis. Among these was Bcl2a1, an antiapoptotic Bcl2 family member. Quantitative real-time PCR analysis confirmed this finding and demon- strated that Bcl2a1 mRNA expression was significantly greater in nonapoptotic than in apoptotic T lymphocytes. The RXR agonist 9-cis-retinoic acid also increased Bcl2a1 expression, although all-trans-retinoic acid and ligands for other RXR partner receptors did not. Treatment with AGN194204 and 9-cis-retinoic acid significantly decreased apoptosis measured by annexin V staining but did not affect expression of Bcl2 and Bcl-xL. Bcl2a1 promoter activity was examined using a luciferase promoter construct. Both AGN194204 and 9-cis-retinoic acid significantly increased luciferase activity. In summary, these data demonstrate that RXR agonists increase Bcl2a1 promoter activity and increase expression of Bcl2a1 in naive T lymphocytes but do not affect Bcl2 and Bcl-xL expression in naive T lymphocytes.
    [Show full text]
  • CD98 at the Crossroads of Adaptive Immunity and Cancer
    Commentary 1373 CD98 at the crossroads of adaptive immunity and cancer Joseph M. Cantor1 and Mark H. Ginsberg1,* Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA *Author for correspondence ([email protected]) Journal of Cell Science 125, 1373–1382 ß 2012. Published by The Company of Biologists Ltd doi: 10.1242/jcs.096040 Summary Adaptive immunity, a vertebrate specialization, adds memory and exquisite specificity to the basic innate immune responses present in invertebrates while conserving metabolic resources. In adaptive immunity, antigenic challenge requires extremely rapid proliferation of rare antigen-specific lymphocytes to produce large, clonally expanded effector populations that neutralize pathogens. Rapid proliferation and resulting clonal expansion are dependent on CD98, a protein whose well-conserved orthologs appear restricted to vertebrates. Thus, CD98 supports lymphocyte clonal expansion to enable protective adaptive immunity, an advantage that could account for the presence of CD98 in vertebrates. CD98 supports lymphocyte clonal expansion by amplifying integrin signals that enable proliferation and prevent apoptosis. These integrin-dependent signals can also provoke cancer development and invasion, anchorage-independence and the rapid proliferation of tumor cells. CD98 is highly expressed in many cancers and contributes to formation of tumors in experimental models. Strikingly, vertebrates, which possess highly conserved CD98 proteins, CD98-binding integrins and adaptive immunity, also display propensity towards invasive and metastatic tumors. In this Commentary, we review the roles of CD98 in lymphocyte biology and cancer. We suggest that the CD98 amplification of integrin signaling in adaptive immunity provides survival benefits to vertebrates, which, in turn, bear the price of increased susceptibility to cancer.
    [Show full text]
  • Mouse CD Marker Chart Bdbiosciences.Com/Cdmarkers
    BD Mouse CD Marker Chart bdbiosciences.com/cdmarkers 23-12400-01 CD Alternative Name Ligands & Associated Molecules T Cell B Cell Dendritic Cell NK Cell Stem Cell/Precursor Macrophage/Monocyte Granulocyte Platelet Erythrocyte Endothelial Cell Epithelial Cell CD Alternative Name Ligands & Associated Molecules T Cell B Cell Dendritic Cell NK Cell Stem Cell/Precursor Macrophage/Monocyte Granulocyte Platelet Erythrocyte Endothelial Cell Epithelial Cell CD Alternative Name Ligands & Associated Molecules T Cell B Cell Dendritic Cell NK Cell Stem Cell/Precursor Macrophage/Monocyte Granulocyte Platelet Erythrocyte Endothelial Cell Epithelial Cell CD1d CD1.1, CD1.2, Ly-38 Lipid, Glycolipid Ag + + + + + + + + CD104 Integrin b4 Laminin, Plectin + DNAX accessory molecule 1 (DNAM-1), Platelet and T cell CD226 activation antigen 1 (PTA-1), T lineage-specific activation antigen 1 CD112, CD155, LFA-1 + + + + + – + – – CD2 LFA-2, Ly-37, Ly37 CD48, CD58, CD59, CD15 + + + + + CD105 Endoglin TGF-b + + antigen (TLiSA1) Mucin 1 (MUC1, MUC-1), DF3 antigen, H23 antigen, PUM, PEM, CD227 CD54, CD169, Selectins; Grb2, β-Catenin, GSK-3β CD3g CD3g, CD3 g chain, T3g TCR complex + CD106 VCAM-1 VLA-4 + + EMA, Tumor-associated mucin, Episialin + + + + + + Melanotransferrin (MT, MTF1), p97 Melanoma antigen CD3d CD3d, CD3 d chain, T3d TCR complex + CD107a LAMP-1 Collagen, Laminin, Fibronectin + + + CD228 Iron, Plasminogen, pro-UPA (p97, MAP97), Mfi2, gp95 + + CD3e CD3e, CD3 e chain, CD3, T3e TCR complex + + CD107b LAMP-2, LGP-96, LAMP-B + + Lymphocyte antigen 9 (Ly9),
    [Show full text]
  • Anti-CD98 Heavy Chain [HBJ127] Standard Size, 200 Μg, Ab00794-23.0 View Online
    Anti-CD98 heavy chain [HBJ127] Standard Size, 200 μg, Ab00794-23.0 View online Anti-CD98 heavy chain [HBJ127] Standard Size Ab00794-23.0 This chimeric rabbit antibody was made using the variable domain sequences of the original Mouse IgG1 format, for improved compatibility with existing reagents, assays and techniques. Isotype and Format: Rabbit IgG, Kappa Clone Number: HBJ127 Alternative Name(s) of Target: 4F2hc; HBJ 127; HBJ-127; CD98; GP125; 4F2 cell-surface antigen heavy chain; 4F2 heavy chain antigen; Lymphocyte activation antigen 4F2 large subunit; Solute carrier family 3 member 2 UniProt Accession Number of Target Protein: P08195 Published Application(s): Activate, Block, ELISA, IF Published Species Reactivity: Human Immunogen: HBJ127 was obtained from hybridomas generated by the fusion of mouse myeloma cells and spleen cells from mice which had been immunized with T24 hyman bladder cancer cells. Specificity: HBJ127 binds to the CD98 heavy chain at an epitope consisting of residues AFS (aa 442-444) (Itoh et al, 2007). The antibody has not been shown to cross-react with other species. CD98 is expressed at high levels on monocytes and at very low level on peripheral blood T and B lymphocytes, splenocytes, NK cells and granulocytes. CD98 is a disulfide-linked and glycosylated type II integral membrane protein. This protein has roles in normal and neoplastic cell growth and is required for the function of light chain amino acid transporters. It is also involved in sodium-independent transport of large neitral amino acids and in guiding and targeting LAT1 and LAT2 to the plasma membrane. When associated with SLC7A6 or SLC7A7, CD98 acts as an arginine/glutamine exchanger.
    [Show full text]
  • Approaches to CNS Drug Delivery with a Focus on Transporter-Mediated Transcytosis
    International Journal of Molecular Sciences Review Approaches to CNS Drug Delivery with a Focus on Transporter-Mediated Transcytosis Rana Abdul Razzak 1,2, Gordon J. Florence 2 and Frank J. Gunn-Moore 1,2,* 1 Medical and Biological Sciences Building, School of Biology, University of St Andrews, St Andrews KY16 9TF, UK; [email protected] 2 Biomedical Science Research Centre, Schools of Chemistry and Biology, University of St Andrews, St Andrews KY16 9TF, UK; [email protected] * Correspondence: [email protected]; Tel.: +44-1334-463525 Received: 27 May 2019; Accepted: 16 June 2019; Published: 25 June 2019 Abstract: Drug delivery to the central nervous system (CNS) conferred by brain barriers is a major obstacle in the development of effective neurotherapeutics. In this review, a classification of current approaches of clinical or investigational importance for the delivery of therapeutics to the CNS is presented. This classification includes the use of formulations administered systemically that can elicit transcytosis-mediated transport by interacting with transporters expressed by transvascular endothelial cells. Neurotherapeutics can also be delivered to the CNS by means of surgical intervention using specialized catheters or implantable reservoirs. Strategies for delivering drugs to the CNS have evolved tremendously during the last two decades, yet, some factors can affect the quality of data generated in preclinical investigation, which can hamper the extension of the applications of these strategies into clinically useful tools. Here, we disclose some of these factors and propose some solutions that may prove valuable at bridging the gap between preclinical findings and clinical trials.
    [Show full text]