title: The nucleoporin Nup88 is interacting with nuclear lamin A.
abstract: Nuclear pore complexes (NPCs) are embedded in the nuclear envelope (NE) and mediate bidirectional nucleocytoplasmic transport. Their spatial distribution in the NE is organized by the nuclear lamina, a meshwork of nuclear intermediate filament proteins. Major constituents of the nuclear lamina are A- and B-type lamins. In this work we show that the nuclear pore protein Nup88 binds lamin A in vitro and in vivo. The interaction is mediated by the N-terminus of Nup88, and Nup88 specifically binds the tail domain of lamin A but not of lamins B1 and B2. Expression of green fluorescent protein-tagged lamin A in cells causes a masking of binding sites for Nup88 antibodies in immunofluorescence assays, supporting the interaction of lamin A with Nup88 in a cellular context. The epitope masking disappears in cells expressing mutants of lamin A that are associated with laminopathic diseases. Consistently, an interaction of Nup88 with these mutants is disrupted in vitro. Immunoelectron microscopy using Xenopus laevis oocyte nuclei further revealed that Nup88 localizes to the cytoplasmic and nuclear face of the NPC. Together our data suggest that a pool of Nup88 on the nuclear side of the NPC provides a novel, unexpected binding site for nuclear lamin A.
authors.affiliation: M.E. Müller Institute for Structural Biology, Biozentrum, University of Basel, 4056 Basel, Switzerland.
authors.forename: Yvonne C
authors.initials: YC
authors.lastname: Lussi
authors.forename: Ilona
authors.initials: I
authors.lastname: Hügi
authors.forename: Eva
authors.initials: E
authors.lastname: Laurell
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kutay
authors.forename: Birthe
authors.initials: B
authors.lastname: Fahrenkrog
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism / Q000648:ultrastructure; D022022:Nuclear Pore / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D034904:Lamin Type A; C104835:NUP88 protein, human; D028861:Nuclear Pore Complex Proteins; D011993:Recombinant Fusion Proteins