| First Author | Massaeli H | Year | 2019 |
| Journal | Biochim Biophys Acta Mol Cell Res | Volume | 1866 |
| Issue | 4 | Pages | 727-736 |
| PubMed ID | 30529231 | Mgi Jnum | J:274341 |
| Mgi Id | MGI:6294816 | Doi | 10.1016/j.bbamcr.2018.12.003 |
| Citation | Massaeli H, et al. (2019) Endoplasmic reticulum stress enhances endocytosis in calreticulin deficient cells. Biochim Biophys Acta Mol Cell Res 1866(4):727-736 |
| abstractText | Calreticulin an endoplasmic reticulum (ER) chaperone that is involved in the quality control process and plays an important role as a regulator of intracellular calcium homeostasis. Previously, we illustrated that loss of calreticulin (crt-/-) results in the activation of ubiquitin-proteasome pathway facilitating the increased resistance to apoptosis. Our preliminary data illustrated a significant increase in the endocytosis in the calreticulin knockout mouse embryonic fibroblast cells (crt-/-). Therefore, we hypothesized that the mechanism for this increased endocytosis in the crt-/- cells is due to onset of ER stress. To test this hypothesis, we measured endocytosis in the wild type (wt) and crt-/- cells using uptake of fluorescent dextran and showed a significant increase in the rate of its uptake in crt-/- cells as compared to wt cells. To determine the endocytic pathway involved we examined both clathrin and caveolin-1 dependent endocytosis. Our results illustrated no change in the expression of clathrin heavy chain while there was a significant increase in the expression of caveolin-1 in the crt-/- cells as compared to the wt cells. Furthermore, using shRNA we illustrated that knockdown of clathrin heavy chain had no effect on endocytosis in the crt-/- cells. While knock-down of caveolin-1 significantly reduced endocytosis in the crt-/- cells. Finally, we illustrated that a chemical chaperone, 4phenylbutyrate significantly reduced both the endoplasmic reticulum stress and endocytosis in the crt-/- cells. Our data shows for the first time, that ER stress led to enhanced caveolin-1 mediated endocytosis and reversal of ER stress reduces endocytosis. |
