Bap29/31 Influences the Intracellular Traffic of MHC Class I Molecules

Abstract

In this study, we examine the role of the putative cargo receptor B cell-associated protein (Bap)29/31 in the export of MHC class I molecules out of the endoplasmic reticulum (ER). We show that Bap31 binds to two allotypes of mouse class I molecules, with the interaction initiated at the time of H chain association with β2-microglobulin and maintained until the class I molecule has left the ER. We also show that Bap31 is part of the peptide-loading complex, although is not required for its formation. Bap31 binds not only to class I molecules, but can bind to tapasin in the absence of class I. Consistent with an important role in recruiting class I molecules to transport vesicles, we show that in the absence of Bap29/31, there is a loss of class I colocalization with mSec31 (p137), a component of mammalian coat protein complex II coats. This observation is also associated with a delay in class I traffic from ER to Golgi. Our results are consistent with the view that class I molecules are largely recruited to ER exit sites by Bap29/31, and that Bap29/31 is a cargo receptor for MHC class I molecules.

The Double Lysine Motif of Tapasin Is a Retrieval Signal for Retention of Unstable MHC Class I Molecules in the Endoplasmic Reticulum

“…However, most of the studied ER proteins with KKXX mutations have been shown to increase their distribution in post-ER compartments (18,37). Although tpn is an ER residential molecule, a proportion of tpn is detected in the Golgi (4) and tpn interacts with an ER export receptor (38), supporting the notion that tpn could escape from the ER. The association of COPI coatomer with tpn indicates that these escaped tpn are retrograde transported back to the ER by COPI-coated vesicles (4).…”

Tapasin-related protein TAPBPR is an additional component of the MHC class I presentation pathway

“…Post-PLC, MHC I molecules are exported from the ER via a selective process, involving trafficking motifs in the HC cytoplasmic tails and Bap31, which facilitates recruitment into COP-II coated vesicles (31)(32)(33)(34)(35)(36). A bottleneck in the MHC I pathway appears to occur before the medial Golgi with the transport of suboptimally loaded MHC I molecules and PLC components blocked at this step (4,(37)(38)(39)(40).…”

MHC Class I Quality Control

“…This ensures the release of only stable pMHC-I complexes to the cell surface, which is vital for the subsequent CTL scrutiny. The pMHC-I transportation to the cell surface has been suggested to start with packaging of the pMHC-I complexes in COPII vesicles, which then migrate to the Golgi apparatus, and then further on to the cell surface (Paquet, Cohen-Doyle et al 2004). The following sections discuss the MHC-I maturation, and peptide supply in much more detail.…”