Genetic and molecular interactions of the Erv41p-Erv46p complex involved in transport between the endoplasmic reticulum and Golgi complex

Abstract

Erv41p and Erv46p are integral membrane proteins conserved across species. They were originally identified as abundant constituents of COPII-coated vesicles, and form a complex which cycles between the endoplasmic reticulum and Golgi complex. Yeast strains lacking these proteins are viable but display subtle secretory phenotypes. In order to obtain information about possible biological roles of this protein complex in endoplasmic reticulum to Golgi transport, we employed the Synthetic Genetic Array approach to screen for synthetic genetic interactions with the erv46 null mutation. We identified synthetic interactions with vma12, vma21, vma22 and vps1 deletion mutations. The vma21Δ mutation exacerbates transport defects caused by the erv46Δ mutation. Unexpectedly, yeast strains lacking Vma21p fail to sort the endoplasmic reticulum to Golgi v-SNARE, Bos1p, efficiently into COPII vesicles, yet these vesicles are fully fusion competent. In addition, we set out to identify, by a biochemical approach, proteins interacting with the Erv41p-Erv46p complex. We report a strong interaction between the Erv41p-Erv46p complex and endoplasmic reticulum glucosidase II. Strains lacking a cycling Erv41p-Erv46p complex display a mild glycoprotein processing defect.

Molecular Characterization and Expression Profiling of the Protein Disulfide Isomerase Gene Family in Brachypodium distachyon L

“…An endoplasmic reticulum-Golgi intermediate compartment (ERGIC) domain was located in the N-terminus, and an endoplasmic reticulum vesicle transporter domain (COPII coated_ERV) was located in the C-terminus. These domains are also present in several other proteins, such as ERGIC-32 in mouse and Erv41p and Erv46p in yeast, and play important roles in protein sorting, folding, and glycoprotein processing in the ER and early Golgi complex [39], [40]. The functions of two trans-membrane regions of the BdPDIL8-1 are assumed to replace the function of the N-terminal signal peptide and C-terminal KDEL retrieval sequence, both of which are involved in the early protein secretory pathway between ER, ERGIC, and the Golgi complex.…”

Suppression subtractive hybridization identified differentially expressed genes in lung adenocarcinoma: ERGIC3as a novel lung cancer-related gene

“…ERGIC3 has large domains in the ER lumen, and its short N- and C-terminal tail sequences expose to the cytosol and the two transmembrane segments each, which would be available for protein-protein interactions in the ER lumen or membrane [26]. Through the systematic and serial screening, we found that the ERGIC3 mRNA and protein were highly over-expressed in lung cancer cells.…”

ERGIC3 (ERGIC and golgi 3)

“…ERGIC3 belongs to the family of the ER vesicle (Erv) proteins (Otte et al, 2001). ERGIC3 interacts with ERGIC2 (Welsh et al, 2006) and ERGIC1 (Breuza et al, 2004) and forms a heterotrimeric protein complex. Both isoforms contain ERGIC_N domain and COPIIcoated_ERV domain (figure 3) which is conserved from fungi to humans.…”

“…ERGIC3 works in close on junction with ERGIC2 and together they form a complex which cycles between the endoplasmic reticulum and cis-Golgi network. Both are integral membrane proteins with two membrane spanning segments each, short Nand C-terminal tails expose to the cytosol, and large central luminal domains (figure 3) (Welsh et al, 2006). …”

“…There is a strong interaction between ERGIC3 and ERGIC2 so as to form a heteromer complex which exerting its biological function. The complex may be involved in : 1) the sorting of some secretory molecules during vesiclar transport (Belden and Barlowe, 2001;Otte and Barlowe, 2004) due to the hydrophobic signals present on both C-terminal tails of the ERGIC3-ERGIC2 complex control sorting into COPII vesicles for anterograde transport, and retrieval from the Golgi is mediated by a COPI binding KKxx motif on ERGIC3 (Otte and Barlowe, 2002) ; 2) protein folding and glycoprotein processing in the endoplasmic reticulum and cis-Golgi network (Nishikawa et al, 2007;Welsh et al, 2006). Glucosidase II is not transported into COPII vesicles in vitro as well as cells lacking a cycling ERGIC3-ERGIC2 complex have a mild glycoprotein processing defect and a partial loss of glucosidase (Leah, 2006) inhibiting endoplasmic reticulum stress (ERS)-induced cell death by tunicamycin in HEK-293 cells (Nishikawa et al, 2007).…”