title: Clathrin inhibitor Pitstop-2 disrupts the nuclear pore complex permeability barrier.
abstract: 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.
authors.affiliation: Institute of Physiology II, Robert-Koch-Str. 27b, 48149 Münster, Germany.
authors.forename: Ivan
authors.initials: I
authors.lastname: Liashkovich
authors.affiliation: Institute of Physiology II, Robert-Koch-Str. 27b, 48149 Münster, Germany.
authors.forename: Dzmitry
authors.initials: D
authors.lastname: Pasrednik
authors.affiliation: Institute of Physiology II, Robert-Koch-Str. 27b, 48149 Münster, Germany.
authors.forename: Valeria
authors.initials: V
authors.lastname: Prystopiuk
authors.affiliation: Institute of Physiology II, Robert-Koch-Str. 27b, 48149 Münster, Germany.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Rosso
authors.affiliation: Institute of Physiology II, Robert-Koch-Str. 27b, 48149 Münster, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Oberleithner
authors.affiliation: Institute of Physiology II, Robert-Koch-Str. 27b, 48149 Münster, Germany.
authors.forename: Victor
authors.initials: V
authors.lastname: Shahin
mesh_terms: D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D002966:Clathrin / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D022022:Nuclear Pore / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*; D053778:Thiazolidines / Q000494:pharmacology*; D028961:beta Karyopherins / Q000378:metabolism*
chemical_list: D002966:Clathrin; D013449:Sulfonamides; D053778:Thiazolidines; D028961:beta Karyopherins; C578512:pitstop 2