Publikation:

Inhibition of clathrin-mediated endocytosis by knockdown of AP-2 leads to alterations in the plasma membrane proteome

Lade...
Vorschaubild

Dateien

Tobys_2-ua285e5dtsmx4.pdf
Tobys_2-ua285e5dtsmx4.pdfGröße: 5.11 MBDownloads: 247

Datum

2021

Autor:innen

Tobys, David
Kowalski, Lisa Maria
Cziudaj, Eva
Müller, Stefan
Zentis, Peter
Pach, Elke
Zigrino, Paola
Höning, Stefan

Herausgeber:innen

Kontakt

ISSN der Zeitschrift

Electronic ISSN

ISBN

Bibliografische Daten

Verlag

Schriftenreihe

Auflagebezeichnung

DOI (zitierfähiger Link)
ArXiv-ID

Internationale Patentnummer

Link zur Lizenz

Angaben zur Forschungsförderung

Projekt

Open Access-Veröffentlichung
Open Access Hybrid
Core Facility der Universität Konstanz

Gesperrt bis

Titel in einer weiteren Sprache

Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published

Erschienen in

Traffic. Wiley-Blackwell. 2021, 22(1-2), pp. 6-22. ISSN 1398-9219. eISSN 1600-0854. Available under: doi: 10.1111/tra.12770

Zusammenfassung

In eukaryotic cells, clathrin-mediated endocytosis (CME) is a central pathway for the internalization of proteins from the cell surface, thereby contributing to the maintenance of the plasma membrane protein composition. A key component for the formation of endocytic clathrin-coated vesicles (CCVs) is AP-2, as it sequesters cargo membrane proteins, recruits a multitude of other endocytic factors and initiates clathrin polymerization. Here, we inhibited CME by depletion of AP-2 and explored the consequences for the plasma membrane proteome. Quantitative analysis revealed accumulation of major constituents of the endosomal-lysosomal system reflecting a block in retrieval by compensatory CME. The noticeable enrichment of integrins and blockage of their turnover resulted in severely impaired cell migration. Rare proteins such as the anti-cancer drug target CA9 and tumor markers (CD73, CD164, CD302) were significantly enriched. The AP-2 knockdown attenuated the global endocytic capacity, but clathrin-independent entry pathways were still operating, as indicated by persistent internalization of specific membrane-spanning and GPI-anchored receptors (PVR, IGF1R, CD55, TNAP). We hypothesize that blocking AP-2 function and thus inhibiting CME may be a novel approach to identify new druggable targets, or to increase their residence time at the plasma membrane, thereby increasing the probability for efficient therapeutic intervention.

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

Konferenz

Rezension
undefined / . - undefined, undefined

Forschungsvorhaben

Organisationseinheiten

Zeitschriftenheft

Zugehörige Datensätze in KOPS

Zitieren

ISO 690TOBYS, David, Lisa Maria KOWALSKI, Eva CZIUDAJ, Stefan MÜLLER, Peter ZENTIS, Elke PACH, Paola ZIGRINO, Tobias BLÄSKE, Stefan HÖNING, 2021. Inhibition of clathrin-mediated endocytosis by knockdown of AP-2 leads to alterations in the plasma membrane proteome. In: Traffic. Wiley-Blackwell. 2021, 22(1-2), pp. 6-22. ISSN 1398-9219. eISSN 1600-0854. Available under: doi: 10.1111/tra.12770
BibTex
@article{Tobys2021-01Inhib-52302,
  year={2021},
  doi={10.1111/tra.12770},
  title={Inhibition of clathrin-mediated endocytosis by knockdown of AP-2 leads to alterations in the plasma membrane proteome},
  number={1-2},
  volume={22},
  issn={1398-9219},
  journal={Traffic},
  pages={6--22},
  author={Tobys, David and Kowalski, Lisa Maria and Cziudaj, Eva and Müller, Stefan and Zentis, Peter and Pach, Elke and Zigrino, Paola and Bläske, Tobias and Höning, Stefan}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/52302">
    <dc:creator>Tobys, David</dc:creator>
    <dc:contributor>Zigrino, Paola</dc:contributor>
    <dc:rights>Attribution-NonCommercial-NoDerivatives 4.0 International</dc:rights>
    <dc:contributor>Bläske, Tobias</dc:contributor>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by-nc-nd/4.0/"/>
    <dc:creator>Pach, Elke</dc:creator>
    <dc:creator>Kowalski, Lisa Maria</dc:creator>
    <dc:contributor>Höning, Stefan</dc:contributor>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/52302/1/Tobys_2-ua285e5dtsmx4.pdf"/>
    <dc:contributor>Pach, Elke</dc:contributor>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-01-07T10:26:19Z</dc:date>
    <dc:language>eng</dc:language>
    <dc:creator>Müller, Stefan</dc:creator>
    <dc:contributor>Müller, Stefan</dc:contributor>
    <dc:creator>Zentis, Peter</dc:creator>
    <dc:creator>Zigrino, Paola</dc:creator>
    <dcterms:issued>2021-01</dcterms:issued>
    <dcterms:abstract xml:lang="eng">In eukaryotic cells, clathrin-mediated endocytosis (CME) is a central pathway for the internalization of proteins from the cell surface, thereby contributing to the maintenance of the plasma membrane protein composition. A key component for the formation of endocytic clathrin-coated vesicles (CCVs) is AP-2, as it sequesters cargo membrane proteins, recruits a multitude of other endocytic factors and initiates clathrin polymerization. Here, we inhibited CME by depletion of AP-2 and explored the consequences for the plasma membrane proteome. Quantitative analysis revealed accumulation of major constituents of the endosomal-lysosomal system reflecting a block in retrieval by compensatory CME. The noticeable enrichment of integrins and blockage of their turnover resulted in severely impaired cell migration. Rare proteins such as the anti-cancer drug target CA9 and tumor markers (CD73, CD164, CD302) were significantly enriched. The AP-2 knockdown attenuated the global endocytic capacity, but clathrin-independent entry pathways were still operating, as indicated by persistent internalization of specific membrane-spanning and GPI-anchored receptors (PVR, IGF1R, CD55, TNAP). We hypothesize that blocking AP-2 function and thus inhibiting CME may be a novel approach to identify new druggable targets, or to increase their residence time at the plasma membrane, thereby increasing the probability for efficient therapeutic intervention.</dcterms:abstract>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/52302/1/Tobys_2-ua285e5dtsmx4.pdf"/>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/52302"/>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-01-07T10:26:19Z</dcterms:available>
    <dc:creator>Cziudaj, Eva</dc:creator>
    <dc:contributor>Kowalski, Lisa Maria</dc:contributor>
    <dc:contributor>Cziudaj, Eva</dc:contributor>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:creator>Höning, Stefan</dc:creator>
    <dcterms:title>Inhibition of clathrin-mediated endocytosis by knockdown of AP-2 leads to alterations in the plasma membrane proteome</dcterms:title>
    <dc:contributor>Zentis, Peter</dc:contributor>
    <dc:contributor>Tobys, David</dc:contributor>
    <dc:creator>Bläske, Tobias</dc:creator>
  </rdf:Description>
</rdf:RDF>

Interner Vermerk

xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter

Kontakt
URL der Originalveröffentl.

Prüfdatum der URL

Prüfungsdatum der Dissertation

Finanzierungsart

Kommentar zur Publikation

Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Ja
Diese Publikation teilen