Vigilin interacts with signal peptide peptidase

Proteome Science

Research

Roger Dodd¹  Katie Cox¹  Yi Li¹  William Meadows¹  Seema Qamar¹  Beth McDonald¹  Stephen Hsueh-Jeng Lu¹  Peter St George-Hyslop²  Fusheng Chen³  Amy Hye Won Jeon³  Gerold Schmitt-Ulms³  Christopher Bohm³  Paul Fraser³ 

[1] Cambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Hills Road, CB2 0XY, England, Cambridge, United Kingdom;Cambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Hills Road, CB2 0XY, England, Cambridge, United Kingdom;Tanz Centre for Research in Neurodegenerative Diseases, and Departments of Medicine, Laboratory Medicine and Pathobiology, and Medical Biophysics, University of Toronto, 6 Queen's Park Crescent West, M5S 3H2, Toronto, ON, Canada;Tanz Centre for Research in Neurodegenerative Diseases, and Departments of Medicine, Laboratory Medicine and Pathobiology, and Medical Biophysics, University of Toronto, 6 Queen's Park Crescent West, M5S 3H2, Toronto, ON, Canada;

关键词: Signal peptide peptidase;    Vigilin;    Biochemistry;    Intramembrane-cleaving aspartyl protease;    Non-proteolytic function;    Interactome;   

DOI  :  10.1186/1477-5956-10-33

 received in 2012-01-16, accepted in 2012-05-04,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundSignal peptide peptidase (SPP), a member of the presenilin-like intra-membrane cleaving aspartyl protease family, migrates on Blue Native (BN) gels as 100 kDa, 200 kDa and 450 kDa species. SPP has recently been implicated in other non-proteolytic functions such as retro-translocation of MHC Class I molecules and binding of misfolded proteins in the endoplasmic reticulum (ER). These high molecular weight SPP complexes might contain additional proteins that regulate the proteolytic activity of SPP or support its non-catalytic functions.ResultsIn this study, an unbiased iTRAQ-labeling mass spectrometry approach was used to identify SPP-interacting proteins. We found that vigilin, a ubiquitous multi-KH domain containing cytoplasmic protein involved in RNA binding and protein translation control, selectively enriched with SPP. Vigilin interacted with SPP and both proteins co-localized in restricted intracellular domains near the ER, biochemically co-fractionated and were part of the same 450 kDa complex on BN gels. However, vigilin does not alter the protease activity of SPP, suggesting that the SPP-vigilin interaction might be involved in the non-proteolytic functions of SPP.ConclusionsWe have identified and validated vigilin as a novel interacting partner of SPP that could play an important role in the non-proteolytic functions of SPP. This data adds further weight to the idea that intramembrane-cleaving aspartyl proteases, such as presenilin and SPPs, could have other functions besides the proteolysis of short membrane stubs.

【 授权许可】

Unknown   
© Lu et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.