CCPG1 Is a Non-canonical Autophagy Cargo Receptor Essential for ER-Phagy and Pancreatic ER Proteostasis

• DOI: 10.1016/j.devcel.2017.11.024
• Publication Date: 2017-12-28T16:38:20Z
• Authors: Matthew D. Smith; Margaret E. Harley; Alain J. Kemp; Jimi Wills; Martin Lee; Mark Arends; Alex von Kriegsheim; Christian Behrends; Simon Wilkinson
• Keywords: Proteostasis; Non canonical

Highlights•CCPG1 is an ER stress-inducible ER-phagy cargo receptor in mammals•CCPG1 binds directly to ATG8 proteins and FIP200 via distinct peptide motifs•CCPG1 lysosomal degradation both require these interactions•CCPG1 maintains normal luminal proteostasis pancreatic acinar cells vivoSummaryMechanisms of selective autophagy the ER, known as ER-phagy, molecular delineation, particularly vivo. It unclear how events control cellular health. Here, we identify cell-cycle progression gene 1 (CCPG1), ER-resident protein with no physiological role, a non-canonical that core LIR motif mammalian and, independently discrete motif, FIP200. These interactions facilitate ER-phagy. The CCPG1 inducible by unfolded response thus links stress In vivo, protects against aggregation consequent hyperactivation tissue injury exocrine pancreas. Thus, identification this protein, describe unexpected mechanism provide evidence may be physiologically relevant proteostasis.Graphical abstract