Nuclear Membrane Proteins with Potential Disease Links Found by Subtractive Proteomics

TLDR

The study aimed to comprehensively identify integral membrane proteins of the nuclear envelope by preparing isolated NE fractions and cofractionating organelles from liver. Using multidimensional protein identification technology, proteins from cofractionating organelles were subtracted from the NE dataset to isolate true NE components. We discovered 67 novel NE integral proteins, all of which localized to the nuclear envelope, and 23 of these reside in chromosomal regions linked to dystrophies, indicating a larger NE proteome than previously recognized.

Abstract

To comprehensively identify integral membrane proteins of the nuclear envelope (NE), we prepared separately NEs and organelles known to cofractionate with them from liver. Proteins detected by multidimensional protein identification technology in the cofractionating organelles were subtracted from the NE data set. In addition to all 13 known NE integral proteins, 67 uncharacterized open reading frames with predicted membrane-spanning regions were identified. All of the eight proteins tested targeted to the NE, indicating that there are substantially more integral proteins of the NE than previously thought. Furthermore, 23 of these mapped within chromosome regions linked to a variety of dystrophies.