title: Vigilin interacts with signal peptide peptidase.
abstract: BACKGROUND
  Signal 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  We 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.
authors.affiliation: Cambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Hills Road, England, Cambridge, CB2 0XY, United Kingdom. phs22@cam.ac.uk.
authors.forename: Stephen Hsueh-Jeng
authors.initials: SH
authors.lastname: Lu
authors.forename: Amy Hye Won
authors.initials: AH
authors.lastname: Jeon
authors.forename: Gerold
authors.initials: G
authors.lastname: Schmitt-Ulms
authors.forename: Seema
authors.initials: S
authors.lastname: Qamar
authors.forename: Roger
authors.initials: R
authors.lastname: Dodd
authors.forename: Beth
authors.initials: B
authors.lastname: McDonald
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: William
authors.initials: W
authors.lastname: Meadows
authors.forename: Katie
authors.initials: K
authors.lastname: Cox
authors.forename: Christopher
authors.initials: C
authors.lastname: Bohm
authors.forename: Fusheng
authors.initials: F
authors.lastname: Chen
authors.forename: Paul
authors.initials: P
authors.lastname: Fraser
authors.forename: Peter St
authors.initials: PS
authors.lastname: George-Hyslop