title: Recruitment of functionally distinct membrane proteins to chromatin mediates nuclear envelope formation in vivo.
abstract: Formation of the nuclear envelope (NE) around segregated chromosomes occurs by the reshaping of the endoplasmic reticulum (ER), a reservoir for disassembled nuclear membrane components during mitosis. In this study, we show that inner nuclear membrane proteins such as lamin B receptor (LBR), MAN1, Lap2beta, and the trans-membrane nucleoporins Ndc1 and POM121 drive the spreading of ER membranes into the emerging NE via their capacity to bind chromatin in a collaborative manner. Despite their redundant functions, decreasing the levels of any of these trans-membrane proteins by RNAi-mediated knockdown delayed NE formation, whereas increasing the levels of any of them had the opposite effect. Furthermore, acceleration of NE formation interferes with chromosome separation during mitosis, indicating that the time frame over which chromatin becomes membrane enclosed is physiologically relevant and regulated. These data suggest that functionally distinct classes of chromatin-interacting membrane proteins, which are present at nonsaturating levels, collaborate to rapidly reestablish the nuclear compartment at the end of mitosis.
authors.affiliation: Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, La Jolla, CA 92037, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Anderson
authors.forename: Jesse D
authors.initials: JD
authors.lastname: Vargas
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Hsiao
authors.forename: Martin W
authors.initials: MW
authors.lastname: Hetzer
mesh_terms: D002460:Cell Line; D020090:Chromosome Segregation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D009685:Nuclear Envelope / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000097682:Lamin B Receptor
chemical_list: D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D019913:Nuclear Localization Signals; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D000097682:Lamin B Receptor; C405329:LEMD3 protein, human; C510249:NDC1 protein, human; C094157:POM121 protein, human; C529565:SYNE3 protein, human; C093413:lamina-associated polypeptide 2