title: A change in nuclear pore complex composition regulates cell differentiation.
abstract: Nuclear pore complexes (NPCs) are built from ∼30 different proteins called nucleoporins or Nups. Previous studies have shown that several Nups exhibit cell-type-specific expression and that mutations in NPC components result in tissue-specific diseases. Here we show that a specific change in NPC composition is required for both myogenic and neuronal differentiation. The transmembrane nucleoporin Nup210 is absent in proliferating myoblasts and embryonic stem cells (ESCs) but becomes expressed and incorporated into NPCs during cell differentiation. Preventing Nup210 production by RNAi blocks myogenesis and the differentiation of ESCs into neuroprogenitors. We found that the addition of Nup210 to NPCs does not affect nuclear transport but is required for the induction of genes that are essential for cell differentiation. Our results identify a single change in NPC composition as an essential step in cell differentiation and establish a role for Nup210 in gene expression regulation and cell fate determination.
authors.affiliation: Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA. maximiliano.dangelo@ucsf.edu
authors.forename: Maximiliano A
authors.initials: MA
authors.lastname: D'Angelo
authors.forename: J Sebastian
authors.initials: JS
authors.lastname: Gomez-Cavazos
authors.forename: Arianna
authors.initials: A
authors.lastname: Mei
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Lackner
authors.forename: Martin W
authors.initials: MW
authors.lastname: Hetzer
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D051379:Mice; D024510:Muscle Development / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D022022:Nuclear Pore / Q000502:physiology*; D028861:Nuclear Pore Complex Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D028861:Nuclear Pore Complex Proteins; C512902:Nup210 protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering