Page 49 - F. Cell biology

Cytosolic RETREC-X mediates ER-phagy via CKAP4 under ER stress

and regulates tumorigenesis
1
1
Cathena Meiling Li , Jaemin Kang , Youbin Kim , Yong-Keun Jung 1
1
1, School of biological sicences, Seoul National University
BACKGROUND AIM

The endoplasmic reticulum (ER), the largest membranous organelle in the cell, is the place of We designed a gain-of-function screen to identify a new ER-phagy receptor, which
protein synthesis and folding, lipid synthesis, ca2+ storage, detoxification, etc. As ER impacts on regulating ER-phagy under ER stress. This study focuses on elucidating
homeostasis is crucial for cell fate, ER should to be turned over in a regulated way. Although molecular mechanism of RETREC-X-dependent ER-phagy under ER stress.
there are two major cellular degradation processes, ubiquitin-proteasome system (UPS) and
autophagy, it seems like that autophagy has a prominent role in the ER maintenance. Until now,
a few mammalian ER-phagy receptors (FAM134B, SEC62, RTN4L, CCPG1, ATL3, TEX264, and
CALCOCO1) are identified and most of them plays a role in ER-phagy regulation under amino
acid starvation.
RESULTS

CONCLUSION

 In healthy state, CKAP4 binds to
microtubules for maintaining ER shape
and morphology.
REFERENCES
 Under ER stress conditions,
microtubules is detached from CKAP4 An, H., et al. (2019) Molecular cell, 74(5), 891-908.
and RETREC-X homo-oligomers bind Chavda, B., et al. (2017) BMC biochemistry, 18(1), 13.
to CKAP4, which facilitates ER Chen, Q., et al. (2019) Current Biology, 29(5), 846-
turnover through selective autophagy. 855.
Chino, H., et al. (2019) Molecular cell, 74(5), 909-921. ACKNOWLEDGEMENTS
 RETREC-deficiency and CKAP4- Fumagalli, F. et al. (2016) Nature Cell Biology, 18(11),
binding-deficient mutation in RETREC- 1173-1184.
X impair ER-phagy and enhance Grumati, P., et al. (2017) Elife, 6, e25555. Thanks to Noboru Mizushima (Tokyo Univ., Japan) for
tumorigenesis. Khaminets, A. et al. (2015) Nature, 522(7556), 354-8. HeLa/ssRFP-EGFP-KDEL doxycycline inducible cell line,
Nthiga, T. M., et al. (2020) EMBO J. 39(15): 103649. Jin-A Lee (Hannam Univ., Korea) for DNA constructs of GST
tagged LC3/GABARAP, and Atsushi Miyawaki (RIKEN,
Smith, M. D., et al. (2018) Developmental cell, 44(2), Japan) for Keima constructs.
217-232.
Contact information
Cathena Meiling Li
Seoul National University
babycat@snu.ac.kr