Cell-specific and lamin-dependent targeting of novel transmembrane proteins in the nuclear envelope

Poonam Malik, Nadia Korfali, Vlastimil Srsen, Vassiliki Lazou, Dzmitry G Batrakou, Nikolaj Zuleger, Deirdre M Kavanagh, Gavin S Wilkie, Martin W Goldberg, Eric C Schirmer

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)1353-69
Number of pages17
JournalCellular and Molecular Life Sciences
Volume67
Issue number8
DOIs
Publication statusPublished - 2010

Keywords

  • Animals
  • Blotting, Western
  • Cell Nucleus
  • Cells, Cultured
  • Fibroblasts
  • Hepatocytes
  • Humans
  • Kidney
  • Lamin Type A
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Myoblasts
  • Nuclear Envelope
  • Nuclear Proteins
  • Protein Transport
  • Proteomics
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction

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