Li Cathena Meiling, Jung Yong-Keun
School of Biological Sciences, Seoul National University, Seoul, Korea.
Autophagy. 2025 Feb;21(2):490-491. doi: 10.1080/15548627.2024.2431340. Epub 2024 Nov 27.
The endoplasmic reticulum (ER) is the site of multiple cellular events and maintaining its quality control is thus crucial for cell homeostasis. Through a morphology-based gain-of-function screen, we identified the cytosolic protein FKBPL as a regulator of reticulophagy. With multiple protein-binding domains, FKBPL binds to the ER-resident CKAP4, acting as a bridge that connects the ER to the phagophore and facilitating the delivery of ER contents for lysosomal degradation. The FKBPL-CKAP4 axis is essential for both basal and stress-induced reticulophagy. Loss of the FKBPL-CKAP4 interaction attenuates reticulophagy and enhances protein secretion via microvesicle shedding. Here, we propose a dual role for the FKBPL-CKAP4 axis in regulating reticulophagy and protein secretion.
内质网（ER）是多种细胞事件发生的场所，因此维持其质量控制对细胞稳态至关重要。通过基于形态学的功能获得性筛选，我们鉴定出胞质蛋白FKBPL是网织自噬的调节因子。FKBPL具有多个蛋白质结合结构域，它与内质网驻留蛋白CKAP4结合，充当连接内质网与吞噬泡的桥梁，促进内质网内容物向溶酶体的转运以进行降解。FKBPL-CKAP4轴对于基础和应激诱导的网织自噬均至关重要。FKBPL-CKAP4相互作用的丧失会减弱网织自噬，并通过微泡脱落增强蛋白质分泌。在此，我们提出FKBPL-CKAP4轴在调节网织自噬和蛋白质分泌方面具有双重作用。
