Bap31 Enhances the Endoplasmic Reticulum Export and Quality Control of Human Class I MHC Molecules

Ladasky, John J.; Boyle, Sarah; Seth, Malini; Li, Hewang; Pentcheva, Tsvetelina; Abe, Fumiyoshi; Steinberg, Steven J.; Edidin, Michael

doi:10.4049/jimmunol.177.9.6172

Cited by 57 publications

(82 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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).…”

Section: Discussionmentioning

confidence: 99%

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

Boyle

Hermann

Boname

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

106

153

View full text Add to dashboard Cite

Tapasin is an integral component of the peptide-loading complex (PLC) important for efficient peptide loading onto MHC class I molecules. We investigated the function of the tapasin-related protein, TAPBPR. Like tapasin, TAPBPR is widely expressed, IFN-γ-inducible, and binds to MHC class I coupled with β2-microglobulin in the endoplasmic reticulum. In contrast to tapasin, TAPBPR does not bind ERp57 or calreticulin and is not an integral component of the PLC. β2-microglobulin is essential for the association between TAPBPR and MHC class I. However, the association between TAPBPR and MHC class I occurs in the absence of a functional PLC, suggesting peptide is not required. Expression of TAPBPR decreases the rate of MHC class I maturation through the secretory pathway and prolongs the association of MHC class I on the PLC. The TAPBPR: MHC class I complex trafficks through the Golgi apparatus, demonstrating a function of TAPBPR beyond the endoplasmic reticulum/ cis-Golgi. The identification of TAPBPR as an additional component of the MHC class I antigen-presentation pathway demonstrates that mechanisms controlling MHC class I expression remain incompletely understood.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Boyle

Hermann

Boname

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

106

153

View full text Add to dashboard Cite

show abstract

“…Similar comigration was observed for FLAG-tagged Bap31 (data not shown), ruling out the trivial possibility that the ER proteins comigrate with Bap31-mRFP by binding to the mRFP moiety. Given that Bap31 interacts with transmembrane proteins through mutual TMDs (Adachi et al, 1996;Annaert et al, 1997;Spiliotis et al, 2000;Ladasky et al, 2006;Szczesna-Skorupa and Kemper, 2006), it is tempting to speculate that expression of Bap31 may shift the Bap31/interacting proteins equilibrium toward complex formation, leading to comigration of Bap31 and its interacting proteins. It should be noted that juxtanuclear Bap31-mRFP-positive structures could be stained with an ER/mitochondria-staining probe, 3,3Ј-dihexyloxacarbocyanine iodide [DiOC 6 (3)] (Figure 6, fifth row), confirming that Bap31-mRFP at the juxtanuclear region is associated with ER or ER-related membranes.…”

Section: Expression Of Bap31 Induces Comigration Of Er Proteinsmentioning

confidence: 99%

“…Bap31 may function to provide a milieu for efficient folding by recruiting some ER proteins including chaperons (Figure 6). Ladasky et al (2006) recently reported that overexpression of Bap31 increases the cell surface level of class I MHC molecules, whereas Bap29 overexpression rather inhibits class I MHC molecule transport. This result may be relevant to the fact that Bap31 cycles between the juxtanuclear and peripheral regions, whereas Bap29 does not.…”

Section: Possible Implication For Bap31 Cyclingmentioning

confidence: 99%

“…Bap31 and its homologue Bap29 were originally discovered as B cell receptor-associated proteins (Kim et al, 1994). Although solid evidence demonstrated that Bap31 is involved in apoptosis (Breckenridge et al, 2003), accumulating evidence suggest that Bap31 in healthy cells functions as a cargo receptor for ER export of transmembrane proteins, such as cellubrevin, class I major histocompatibility complex (MHC) molecules, CFTR, membrane-bound immunoglobulin (Ig)G, tetraspanins, cytochrome P450 2C2, and the leukocyte integrin CD11b/CD18, some of which are well-known ERAD substrates (Annaert et al, 1997;Spiliotis et al, 2000;Lambert et al, 2001;Schamel et al, 2003;Paquet et al, 2004;Zen et al, 2004;Stojanovic et al, 2005;Ladasky et al, 2006; SzczesnaSkorupa and Kemper, 2006).In the present study, we show that Bap31 is a component of the ER quality control compartment and that it cycles between the peripheral ER and a juxtanuclear ER or an ER-related compartment along microtubule tracks. …”

mentioning

confidence: 99%

See 1 more Smart Citation

Bap31 Is an Itinerant Protein That Moves between the Peripheral Endoplasmic Reticulum (ER) and a Juxtanuclear Compartment Related to ER-associated Degradation

Wakana

Takai

Nakajima

et al. 2008

MBoC

101

View full text Add to dashboard Cite

Certain endoplasmic reticulum (ER)-associated degradation (ERAD) substrates with transmembrane domains are segregated from other ER proteins and sorted into a juxtanuclear subcompartment, known as the ER quality control compartment. Bap31 is an ER protein with three transmembrane domains, and it is assumed to be a cargo receptor for ER export of some transmembrane proteins, especially those prone to ERAD. Here, we show that Bap31 is a component of the ER quality control compartment and that it moves between the peripheral ER and a juxtanuclear ER or ER-related compartment distinct from the conventional ER-Golgi intermediate compartment. The third and second transmembrane domains of Bap31 are principally responsible for the movement to and recycling from the juxtanuclear region, respectively. This cycling was blocked by depolymerization of microtubules and disruption of dynein-dynactin function. Overexpression of Sar1p and Arf1 mutants affected Bap31 cycling, suggesting that this cycling pathway is related to the conventional vesicular transport pathways. INTRODUCTIONThe endoplasmic reticulum (ER) exhibits a reticular tubular network that extends from the nucleus to the cell periphery along microtubule tracks. It performs a variety of functions, including the synthesis, posttranslational modifications, quality control, and export of secretory and membrane proteins; the synthesis of lipids; stress response; Ca 2ϩ storage; and apoptosis. Most, if not all, of these functions are managed by subdomains, such as the rough and smooth ER and transitional ER sites. Each subdomain contains a unique set of proteins that are responsible for its function and organization. ER subdomains are relatively stable, but they can be transformed into alternative structures in response to cellular conditions (for review, see Voeltz et al., 2002;Levine and Rabouille, 2005;Borgese et al., 2006;Vedrenne and Hauri, 2006).Several studies showed the presence of a specialized ER subdomain that is related to ER-associated degradation (ERAD). ERAD is part of a quality control system that ensures the delivery of only correctly folded or assembled secretory and membrane proteins to their final destinations. Newly synthesized proteins that fail to fold or assemble correctly are retained in the ER, retrotranslocated to the cytosol, and degraded by the ubiquitin-proteasome system (for review, see Ellgaard and Helenius, 2003;Meusser et al., 2005;Rö misch, 2005). Studies using mammalian cells demonstrated that transmembrane ERAD substrates are segregated into "ER quality control compartments," which become discernible at the juxtanuclear region upon inhibition of ERAD by proteasome inhibitors (Kamhi-Nesher et al., 2001;Spiliotis et al., 2002). In Saccharomyces cerevisiae, ectopically expressed cystic fibrosis transmembrane conductance regulator (CFTR) is segregated from other ER proteins and accumulates in ER-associated compartments (Kiser et al., 2001;Zhang et al., 2001;Huyer et al., 2004). Degradation of CFTR in yeast is independent of ER-to-Golgi tr...

show abstract

“…In the past decade and a half, numerous studies have found BAP31 associated with various transmembrane proteins, with reported effects on secretory protein biogenesis including ER export (e.g. cellubrevin and major histocompatibility complex I) (15)(16)(17), ER retention (e.g. mIgD) (18), and degradation (e.g.…”

mentioning

confidence: 99%

Yet1p and Yet3p, the Yeast Homologs of BAP29 and BAP31, Interact with the Endoplasmic Reticulum Translocation Apparatus and Are Required for Inositol Prototrophy

Wilson

Barlowe

2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

The mammalian B-cell receptor-associated proteins of 29 and 31 kDa (BAP29 and BAP31) are conserved integral membrane proteins that have reported roles in endoplasmic reticulum (ER) quality control, ER export of secretory cargo, and programmed cell death. In this study we investigated the yeast homologs of BAP29 and BAP31, known as Yet1p and Yet3p, to gain insight on cellular function. We found that Yet1p forms a complex with Yet3p (Yet complex) and that complex assembly was important for subunit stability and proper ER localization. The Yet complex was not efficiently packaged into ER-derived COPII vesicles and therefore does not appear to act as an ER export receptor. Instead, a fraction of the Yet complex was detected in association with the ER translocation apparatus (Sec complex). Specific mutations in the Sec complex or Yet complex influenced these interactions. Moreover, associations between the Yet complex and Sec complex were increased by ER stress and diminished when protein translocation substrates were depleted. Surprisingly, yet1⌬ and yet3⌬ mutant strains displayed inositol starvation-related growth defects. In accord with the biochemical data, these growth defects were exacerbated by a combination of certain mutations in the Sec complex with yet1⌬ or yet3⌬ mutations. We propose a model for the Yet-Sec complex interaction that places Yet1p and Yet3p at the translocation pore to manage biogenesis of specific transmembrane secretory proteins.

show abstract

Bap31 Enhances the Endoplasmic Reticulum Export and Quality Control of Human Class I MHC Molecules

Cited by 57 publications

References 59 publications

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

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

Bap31 Is an Itinerant Protein That Moves between the Peripheral Endoplasmic Reticulum (ER) and a Juxtanuclear Compartment Related to ER-associated Degradation

Yet1p and Yet3p, the Yeast Homologs of BAP29 and BAP31, Interact with the Endoplasmic Reticulum Translocation Apparatus and Are Required for Inositol Prototrophy

Contact Info

Product

Resources

About