title: Nup50 is required for cell differentiation and exhibits transcription-dependent dynamics.
abstract: The nuclear pore complex (NPC) plays a critical role in gene expression by mediating import of transcription regulators into the nucleus and export of RNA transcripts to the cytoplasm. Emerging evidence suggests that in addition to mediating transport, a subset of nucleoporins (Nups) engage in transcriptional activation and elongation at genomic loci that are not associated with NPCs. The underlying mechanism and regulation of Nup mobility on and off nuclear pores remain unclear. Here we show that Nup50 is a mobile Nup with a pronounced presence both at the NPC and in the nucleoplasm that can move between these different localizations. Strikingly, the dynamic behavior of Nup50 in both locations is dependent on active transcription by RNA polymerase II and requires the N-terminal half of the protein, which contains importin α- and Nup153-binding domains. However, Nup50 dynamics are independent of importin α, Nup153, and Nup98, even though the latter two proteins also exhibit transcription-dependent mobility. Of interest, depletion of Nup50 from C2C12 myoblasts does not affect cell proliferation but inhibits differentiation into myotubes. Taken together, our results suggest a transport-independent role for Nup50 in chromatin biology that occurs away from the NPC.
authors.affiliation: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037.
authors.forename: Abigail L
authors.initials: AL
authors.lastname: Buchwalter
authors.affiliation: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037 hetzer@salk.edu.
authors.forename: Martin W
authors.initials: MW
authors.lastname: Hetzer
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002843:Chromatin / Q000235:genetics*; D003593:Cytoplasm / Q000378:metabolism*; D005786:Gene Expression Regulation; D051379:Mice; D022022:Nuclear Pore / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000235:genetics; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D028861:Nuclear Pore Complex Proteins; C513084:Nup153 protein, mouse; C105412:Nup50 protein, mouse; D028901:alpha Karyopherins; D012313:RNA