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 disrup...

Authors: Liashkovich, Ivan
Pasrednik, Dzmitry
Prystopiuk, Valeria
Rosso, Gonzalo
Oberleithner, Hans
Shahin, Victor
Division/Institute:FB 13: Biologie
FB 05: Medizinische Fakultät
Document types:Article
Media types:Text
Publication date:2015
Date of publication on miami:19.11.2015
Modification date:16.04.2019
Edition statement:[Electronic ed.]
Source:Scientific Reports 5 (2015) 9994, 1-9
DDC Subject:610: Medizin und Gesundheit
License:CC BY 4.0
Language:English
Notes:Finanziert durch den Open-Access-Publikationsfonds 2015/2016 der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF document
ISSN:2045-2322
URN:urn:nbn:de:hbz:6-57279462104
Permalink:http://nbn-resolving.de/urn:nbn:de:hbz:6-57279462104
Other Identifiers:DOI: 10.1038/srep09994
Digital documents:srep09994.pdf

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.