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Clathrin inhibitor Pitstop-2 disrupts the nuclear pore complex permeability barrier

Existence of a selective nucleocytoplasmic permeability barrier is attributed to Phenylalanine-Glycine rich proteins (FG-nups) within the central channel of the nuclear pore complex (NPC). Limited understanding of the FG-nup structural arrangement hinders development of strategies directed at disrupting the NPC permeability barrier. In this report we explore an alternative approach to enhancing the NPC permeability for exogenous macromolecules. We demonstrate that the recently discovered inhibitor of clathrin coat assembly Pitstop-2 compromises the NPC permeability barrier in a rapid and effective manner. Treatment with Pitstop-2 causes a collapse of the NPC permeability barrier and a reduction of Importin β binding accompanied by alteration of the NPC ultrastructure. Interestingly, the effects are induced by the same chemical agent that is capable of inhibiting clathrin-mediated endocytosis. To our knowledge, this is the first functional indication of the previously postulated evolutionary relation between clathrin and NPC scaffold proteins.

Titel: Clathrin inhibitor Pitstop-2 disrupts the nuclear pore complex permeability barrier
Verfasser: Liashkovich, Ivan GND
Pasrednik, Dzmitry
Prystopiuk, Valeria GND
Rosso, Gonzalo GND
Oberleithner, Hans
Shahin, Victor GND
Organisation: FB 13: Biologie
FB 05: Medizinische Fakultät
Dokumenttyp: Artikel
Medientyp: Text
Erscheinungsdatum: 06.05.2015
Publikation in MIAMI: 19.11.2015
Datum der letzten Änderung: 16.04.2019
Quelle: Scientific Reports 5 (2015) 9994, 1-9
Fachgebiete: Medizin und Gesundheit
Lizenz: CC BY 4.0
Sprache: Englisch
Anmerkungen: Finanziert durch den Open-Access-Publikationsfonds 2015/2016 der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format: PDF-Dokument
URN: urn:nbn:de:hbz:6-57279462104
Permalink: https://nbn-resolving.org/urn:nbn:de:hbz:6-57279462104
DOI: 10.1038/srep09994
ISSN: 2045-2322
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