Stefanovic, B. and Stefanovic, L. and Schnabl, Bernd and Bataller, R. and Brenner, D. A. (2004) TRAM2 protein interacts with endoplasmic reticulum Ca2+ pump Serca2b and is necessary for collagen type I synthesis. MOLECULAR AND CELLULAR BIOLOGY, 24 (4). pp. 1758-1768. ISSN 0270-7306, 1098-5549
Full text not available from this repository. (Request a copy)Abstract
Cotranslational insertion of type I collagen chains into the lumen of the endoplasmic reticulum (ER) and their subsequent folding into a heterotrimeric helix is a complex process which requires coordinated action of the translation machinery, components of translocons, molecular chaperones, and modifying enzymes. Here we describe a role for the protein TRAM2 in collagen type I expression in hepatic stellate cells (HSCs) and fibroblasts. Activated HSCs are collagen-producing cells in the fibrotic liver. Quiescent HSCs produce trace amounts of type I collagen, while upon activation collagen synthesis increases 50- to 70-fold. Likewise, expression of TRAM2 dramatically increases in activated HSCs. TRAM2 shares 53% amino acid identity with the protein TRAM, which is a component of the translocon. However, TRAM2 has a C terminus with only a 15% identity. The C-terminal part of TRAM2 interacts with the Ca2+ pump of the ER, SERCA2b, as demonstrated in a Saccharomyces cerevisiae two-hybrid screen and by immunoprecipitations in human cells. TRAM2 also coprecipitates with anticollagen antibody, suggesting that these two proteins interact. Deletion of the G terminal part of TRAM2 inhibits type I collagen synthesis during activation of HSCs. The pharmacological inhibitor of SERCA2b, thapsigargin, has a similar effect. Depletion of ER Ca2+ with thapsigargin results in inhibition of triple helical collagen folding and increased intracellular degradation. We propose that TRAM2, as a part of the translocon, is required for the biosynthesis of type I collagen by coupling the activity of SERCA2b with the activity of the translocon. This coupling may increase the local Ca2+ concentration at the site of collagen synthesis, and a high Ca2+ concentration may be necessary for the function of molecular chaperones involved in collagen folding.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEPATIC STELLATE CELLS; MOLECULAR CHAPERONE HSP47; ALPHA-1(I) MESSENGER-RNA; TRIPLE-HELIX FORMATION; FAT-STORING CELLS; DISULFIDE-ISOMERASE; RAT-LIVER; OSTEOGENESIS IMPERFECTA; TRANSLATIONAL CONTROL; EXTRACELLULAR-MATRIX; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Aug 2021 09:00 |
| Last Modified: | 02 Aug 2021 09:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/38046 |
Actions (login required)
 |
View Item |
