The nuclear envelope proteome differs notably between tissues

Abstract

One hypothesis to explain how mutations in the same nuclear envelope proteins yield pathologies focused in distinct tissues is that as yet unidentified tissue-specific partners mediate the disease pathologies. The nuclear envelope proteome was recently determined from leukocytes and muscle. Here the same methodology is applied to liver and a direct comparison of the liver, muscle and leukocyte data sets is presented. At least 74 novel transmembrane proteins identified in these studies have been directly confirmed at the nuclear envelope. Within this set, RT-PCR, western blot and staining of tissue cryosections confirms that the protein complement of the nuclear envelope is clearly distinct from one tissue to another. Bioinformatics reveals similar divergence between tissues across the larger data sets. For proteins acting in complexes according to interactome data, the whole complex often exhibited the same tissue-specificity. Other tissue-specific nuclear envelope proteins identified were known proteins with functions in signaling and gene regulation. The high tissue specificity in the nuclear envelope likely underlies the complex disease pathologies and argues that all organelle proteomes warrant re-examination in multiple tissues.

Keywords: :

• nuclear envelopathies
• nuclear membrane
• organelle proteome
• proteomics
• signaling
• tissue-specific
• transmembrane

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

This study was supported by the Wellcome Trust 076616 and 095209 (E.C.S.) and The Stowers Institute for Medical Research (L.F.). The Wellcome Trust Centre for Cell Biology is supported by core funding from the Wellcome Trust 077707. D.G.B. is a Darwin Trust student. We thank S. Mitchell for assistance with electron microscopy and D. Tollervey and W.C. Earnshaw for comments and discussion.

Supplemental Materials

Supplemental materials may be found here:

http://www.landesbioscience.com/journals/nucleus/article/22257/