Endoplasmic reticulum stress enhances endocytosis in calreticulin deficient cells
| Autor: | Divya Viswanathan, Hamid Massaeli, Nasrin Mesaeli, Dhanya Pillai |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
genetic structures Caveolin 1 Endocytic cycle Endocytosis Clathrin 03 medical and health sciences 0302 clinical medicine medicine Animals Fibroblast Molecular Biology Cells Cultured Mice Knockout biology Chemistry Endoplasmic reticulum Ubiquitination Cell Biology Endoplasmic Reticulum Stress Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis biology.protein Unfolded protein response Chemical chaperone Calreticulin |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1866:727-736 |
| ISSN: | 0167-4889 |
| Popis: | 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, 4‑phenylbutyrate 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. |
| Databáze: | OpenAIRE |
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