title: The Drosophila nucleoporin DNup88 localizes DNup214 and CRM1 on the nuclear envelope and attenuates NES-mediated nuclear export.
abstract: Many cellular responses rely on the control of nucleocytoplasmic transport of transcriptional regulators. The Drosophila nucleoporin Nup88 is selectively required for nuclear accumulation of Rel proteins and full activation of the innate immune response. Here, we investigate the mechanisms underlying its role in nucleocytoplasmic transport. Nuclear import of an nuclear localization signal-enhanced green fluorescent protein (NLS-EGFP) reporter is not affected in DNup88 (members only; mbo) mutants, whereas the level of CRM1-dependent EGFP-nuclear export signal (EGFP-NES) export is increased. We show that the nuclear accumulation of the Drosophila Rel protein Dorsal requires CRM1. DNup88 binds to DNup214 and DCRM1 in vitro, and both proteins become mislocalized from the nuclear rim into the nucleus of mbo mutants. Overexpression of DNup88 is sufficient to relocalize DNup214 and CRM1 on the nuclear envelope and revert the mutant phenotypes. We propose that a major function of DNup88 is to anchor DNup214 and CRM1 on the nuclear envelope and thereby attenuate NES-mediated nuclear export.
authors.affiliation: Department of Developmental Biology, Wenner-Gren Institute, Stockholm University, S-10691 Stockholm, Sweden.
authors.forename: Peggy
authors.initials: P
authors.lastname: Roth
authors.forename: Nikos
authors.initials: N
authors.lastname: Xylourgidis
authors.forename: Nafiseh
authors.initials: N
authors.lastname: Sabri
authors.forename: Anne
authors.initials: A
authors.lastname: Uv
authors.forename: Maarten
authors.initials: M
authors.lastname: Fornerod
authors.forename: Christos
authors.initials: C
authors.lastname: Samakovlis
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins; D028884:Karyopherins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009685:Nuclear Envelope / Q000378:metabolism*; D019913:Nuclear Localization Signals / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D000097606:Exportin 1 Protein
chemical_list: D029721:Drosophila Proteins; D028884:Karyopherins; D019913:Nuclear Localization Signals; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D000097606:Exportin 1 Protein; C490094:Nup214 protein, Drosophila; C062236:dl protein, Drosophila; C491301:mbo protein, Drosophila