title: Cell-specific and lamin-dependent targeting of novel transmembrane proteins in the nuclear envelope.
abstract: Nuclear envelope complexity is expanding with respect to identification of protein components. Here we test the validity of proteomics results that identified 67 novel predicted nuclear envelope transmembrane proteins (NETs) from liver by directly comparing 30 as tagged fusions using targeting assays. This confirmed 21 as NETs, but 4 only targeted in certain cell types, underscoring the complexity of interactions that tether NETs to the nuclear envelope. Four NETs accumulated at the nuclear rim in normal fibroblasts but not in fibroblasts lacking lamin A, suggesting involvement of lamin A in tethering them in the nucleus. However, intriguingly, for the NETs tested alternative mechanisms for nuclear envelope retention could be found in Jurkat cells that normally lack lamin A. This study expands by a factor of three the number of liver NETs analyzed, bringing the total confirmed to 31, and shows that several have multiple mechanisms for nuclear envelope retention.
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Poonam
authors.initials: P
authors.lastname: Malik
authors.forename: Nadia
authors.initials: N
authors.lastname: Korfali
authors.forename: Vlastimil
authors.initials: V
authors.lastname: Srsen
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Lazou
authors.forename: Dzmitry G
authors.initials: DG
authors.lastname: Batrakou
authors.forename: Nikolaj
authors.initials: N
authors.lastname: Zuleger
authors.forename: Deirdre M
authors.initials: DM
authors.lastname: Kavanagh
authors.forename: Gavin S
authors.initials: GS
authors.lastname: Wilkie
authors.forename: Martin W
authors.initials: MW
authors.lastname: Goldberg
authors.forename: Eric C
authors.initials: EC
authors.lastname: Schirmer
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D034904:Lamin Type A / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D021381:Protein Transport; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D034904:Lamin Type A; D008565:Membrane Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C440308:lamin C