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

Abstract

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.

Yet1p–Yet3p interacts with Scs2p–Opi1p to regulate ER localization of the Opi1p repressor

“…Given the phenotypic similarities between the yet1 Δ, yet3 Δ, and scs2 Δ mutants reported earlier in addition to the ER localization of Yet1p, Yet3p, and Scs2p (Kagiwada et al, 1998; Toikkanen et al , 2006; Wilson and Barlowe, 2010), we next examined whether the Yet proteins physically interact with Scs2p and Opi1p. To test for associations, we constructed a strain that expresses chromosomally tagged Scs2p-HA and Opi1p-MYC and performed immunoprecipitation experiments from digitonin solubilized semi-intact cell membranes.…”

Low expression of B‐cell‐associated protein 31 in human primary hepatocellular carcinoma correlates with poor prognosis

“…BAP31 plays roles in the export of secreted proteins in the ER, and in the recognition of abnormally folded proteins and their targeting to the ER‐associated degradation pathway . BAP31 also serves as a cargo receptor for the export of transmembrane proteins . In addition, BAP31 may be involved in caspase 8 (CASP8)‐mediated apoptosis …”

Structural and Biophysical Characterization of the Cytoplasmic Domains of Human BAP29 and BAP31

“…BAP29 is less well studied, but is known to assist or regulate the function of BAP31 in sorting of some clients including IgD [15] and MHC class I molecules [6]. Most client membrane proteins of BAP31 are probably recognized by the transmembrane domain [2], [5], [9], [10], while the C-terminal cytoplasmic region appears to rather play a role in forming interactions with the cytoskeleton [16] and possibly in docking to the translocon, as Yet3p, a yeast homologue of BAP31, has been reported to require the cytoplasmic domain for efficient interaction with the Sec translocon [17]. It may also be noted that although the cytoplasmic domain is not required for binding to cellubrevin, it is needed for its proper sorting [9].…”