| First Author | Ishii S | Year | 2023 |
| Journal | Mol Biol Cell | Volume | 34 |
| Issue | 4 | Pages | ar29 |
| PubMed ID | 36735498 | Mgi Jnum | J:335881 |
| Mgi Id | MGI:7485699 | Doi | 10.1091/mbc.E22-09-0432 |
| Citation | Ishii S, et al. (2023) CCPG1 recognizes endoplasmic reticulum luminal proteins for selective ER-phagy. Mol Biol Cell 34(4):ar29 |
| abstractText | The endoplasmic reticulum (ER) is a major cell compartment where protein synthesis, folding, and posttranslational modifications occur with assistance from a wide variety of chaperones and enzymes. Quality control systems selectively eliminate abnormal proteins that accumulate inside the ER due to cellular stresses. ER-phagy, that is, selective autophagy of the ER, is a mechanism that maintains or reestablishes cellular and ER-specific homeostasis through removal of abnormal proteins. However, how ER luminal proteins are recognized by the ER-phagy machinery remains unclear. Here, we applied the aggregation-prone protein, six-repeated islet amyloid polypeptide (6xIAPP), as a model ER-phagy substrate and found that cell cycle progression 1 (CCPG1), which is an ER-phagy receptor, efficiently mediates its degradation via ER-phagy. We also identified prolyl 3-hydroxylase family member 4 (P3H4) as an endogenous cargo of CCPG1-dependent ER-phagy. The ER luminal region of CCPG1 contains several highly conserved regions that we refer to as cargo-interacting regions (CIRs); these interact directly with specific luminal cargos for ER-phagy. Notably, 6xIAPP and P3H4 interact directly with different CIRs. These findings indicate that CCPG1 is a bispecific ER-phagy receptor for ER luminal proteins and the autophagosomal membrane that contributes to the efficient removal of aberrant ER-resident proteins through ER-phagy. |
