Identification of novel integral membrane proteins of the nuclear envelope with potential disease links using subtractive proteomics

Eric C Schirmer, Laurence Florens, Tinglu Guan, John R Yates, Larry Gerace

Research output: Contribution to journalArticlepeer-review

Abstract

Lamin A and some integral membrane proteins of the nuclear envelope (NE) have been linked to human diseases, mostly dystrophies. To comprehensively identify integral membrane proteins specific to the nuclear envelope, we have carried out a subtractive proteomics analysis of NEs isolated from rodent liver using Multidimensional Protein Identification Technology (MudPIT). An NE fraction and a nucleus-depleted membrane fraction were separately analyzed by MudPIT and proteins appearing in both fractions were 'subtracted' from the NE fraction. This identified 67 novel putative NE transmembrane proteins in addition to the 13 that had been previously characterized. Most or all of the new proteins we identified are likely to be bona fide NE Transmembrane proteins (NETs), since all eight of the first group of proteins we tested in a cell transfection assay target to the NE. Moreover, five of the eight NETs remained associated with the nuclear periphery after extraction with Triton-X100, suggesting an association with the nuclear lamin polymer. 27 of the proteins occur in chromosomal regions where 18 different human dystrophies have been mapped, making these proteins disease candidates. We have analysed the expression of these proteins using transcriptome databases, providing direction for future functional analysis of these novel proteins.
Original languageEnglish
Pages (from-to)63-76; discussion 76-80, 227-30
JournalNovartis Foundation symposium
Volume264
Publication statusPublished - 2005

Keywords

  • Animals
  • Cell Fractionation
  • Chromosome Mapping
  • Genetic Diseases, Inborn
  • Humans
  • Membrane Proteins
  • Nuclear Envelope
  • Nuclear Proteins
  • Proteomics

Fingerprint Dive into the research topics of 'Identification of novel integral membrane proteins of the nuclear envelope with potential disease links using subtractive proteomics'. Together they form a unique fingerprint.

Cite this