| Autor: |
Li, Cathena Meiling, Kang, Jaemin, Baek, Jongyeon, Kim, Youbin, Park, Heemin, Jung, Yong-Keun |
| Předmět: |
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| Zdroj: |
Nature Communications; 9/14/2024, Vol. 15 Issue 1, p1-16, 16p |
| Abstrakt: |
Endoplasmic reticulum quality control is crucial for maintaining cellular homeostasis and adapting to stress conditions. Although several ER-phagy receptors have been identified, the collaboration between cytosolic and ER-resident factors in ER fragmentation and ER-phagy regulation remains unclear. Here, we perform a phenotype-based gain-of-function screen and identify a cytosolic protein, FKBPL, functioning as an ER-phagy regulator. Overexpression of FKBPL triggers ER fragmentation and ER-phagy. FKBPL has multiple protein binding domains, can self-associate and might act as a scaffold connecting CKAP4 and LC3/GABARAPs. CKAP4 serves as a bridge between FKBPL and ER-phagy cargo. ER-phagy-inducing conditions increase FKBPL-CKAP4 interaction followed by FKBPL oligomerization at the ER, leading to ER-phagy. In addition, FKBPL-CKAP4 deficiency leads to Golgi disassembly and lysosome impairment, and an increase in ER-derived secretory vesicles and enhances cytosolic protein secretion via microvesicle shedding. Taken together, FKBPL with the aid of CKAP4 induces ER fragmentation and ER-phagy, and FKBPL-CKAP4 deficiency facilitates protein secretion. ER quality control is crucial to maintain cellular homeostasis. Here, the authors identify a cytosolic ER-phagy regulator inducing ER fragmentation and ER-phagy that functions with an ER-resident receptor, finding a collaboration between cytosolic and ER-resident proteins in quality control. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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