BMC Biology | |
ACBD3 modulates KDEL receptor interaction with PKA for its trafficking via tubulovesicular carrier | |
Pascal Ziltener1  Francesca Bottanelli2  Sunkyu Choi3  Piliang Hao4  Lianhui Zhu4  Mengjing Bao4  Xihua Yue4  Yi Qian4  Intaek Lee5  Yijing Wang6  Chuanting Tan6  Shuaiyang Jing6  Jie Jia6  Bopil Gim7  | |
[1] Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA;Institut für Biochemie, Freie Universität Berlin, Thielallee 63, 14195, Berlin, Germany;Proteomics Core, Weill Cornell Medicine-Qatar, Doha, Qatar;School of Life Science and Technology, ShanghaiTech University, Pudong, Shanghai, China;School of Life Science and Technology, ShanghaiTech University, Pudong, Shanghai, China;Shanghai Institute for Advanced Immunochemical Studies, Shanghai, China;School of Life Science and Technology, ShanghaiTech University, Pudong, Shanghai, China;University of Chinese Academy of Sciences, Beijing, China;School of Physical Science and Technology, ShanghaiTech University, Pudong, Shanghai, China; | |
关键词: KDEL receptor; Protein Kinase A; ACBD3; ArfGAPs; Arf1-GTP; Golgi; | |
DOI : 10.1186/s12915-021-01137-7 | |
来源: Springer | |
【 摘 要 】
BackgroundKDEL receptor helps establish cellular equilibrium in the early secretory pathway by recycling leaked ER-chaperones to the ER during secretion of newly synthesized proteins. Studies have also shown that KDEL receptor may function as a signaling protein that orchestrates membrane flux through the secretory pathway. We have recently shown that KDEL receptor is also a cell surface receptor, which undergoes highly complex itinerary between trans-Golgi network and the plasma membranes via clathrin-mediated transport carriers. Ironically, however, it is still largely unknown how KDEL receptor is distributed to the Golgi at steady state, since its initial discovery in late 1980s.ResultsWe used a proximity-based in vivo tagging strategy to further dissect mechanisms of KDEL receptor trafficking. Our new results reveal that ACBD3 may be a key protein that regulates KDEL receptor trafficking via modulation of Arf1-dependent tubule formation. We demonstrate that ACBD3 directly interact with KDEL receptor and form a functionally distinct protein complex in ArfGAPs-independent manner. Depletion of ACBD3 results in re-localization of KDEL receptor to the ER by inducing accelerated retrograde trafficking of KDEL receptor. Importantly, this is caused by specifically altering KDEL receptor interaction with Protein Kinase A and Arf1/ArfGAP1, eventually leading to increased Arf1-GTP-dependent tubular carrier formation at the Golgi.ConclusionsThese results suggest that ACBD3 may function as a negative regulator of PKA activity on KDEL receptor, thereby restricting its retrograde trafficking in the absence of KDEL ligand binding. Since ACBD3 was originally identified as PAP7, a PBR/PKA-interacting protein at the Golgi/mitochondria, we propose that Golgi-localization of KDEL receptor is likely to be controlled by its interaction with ACBD3/PKA complex at steady state, providing a novel insight for establishment of cellular homeostasis in the early secretory pathway.
【 授权许可】
CC BY
【 预 览 】
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