Page 50 - F. Cell biology

[F. Cell biology-29]

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

stress and regulates tumorigenesis

Cathena Meiling Li¹, Jaemin Kang¹, Youbin Kim¹, Yong-Keun Jung¹

¹School of Biological Sciences, Seoul National University, Seoul 08826, Korea

As an organelle spreads out the cell, endoplasmic reticulum (ER) plays a key role in maintaining cellular homeostasis.
Although 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, six mammalian ER-phagy

receptors (FAM134B, SEC62, RTN4L, CCPG1, ATL3, and TEX264) are known and are all ER-resident membrane proteins.

Here we report that a novel cytosolic protein, reticulophagy regulator X (RETREC-X), plays an essential role in the
ER-phagy under ER stress. RETREC-X binds to a LC3/GABARAP via two LIR motifs in vitro and in cells and
overexpression of RETREC-X triggers ER fission and thereby ER turnover. In contrast, ER mass is increased in the

RETREC-X-deficient cells. RETREC-X is recruited into ER and interacted CKAP4, an ER-shaping protein, on the ER. ER
stress enhances homo-oligomerization of RETREC-X and detachment of CKAP4 from the microtubules, which might

facilitate ER-phagy. Lack of RETREC-X-dependent ER-phagy shows the accumulation of ER and stimulates
tumorigenesis. These results suggest that a cytosolic protein RETREC-X regulates ER-phagy in a CKAP4-dependent

manner under ER stress.