{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chen YJ"],"funding":["NIDDK NIH HHS","NIGMS NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases"],"pagination":["5991"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8514460"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(1)"],"pubmed_abstract":["The reticulon-3 (RTN3)-driven targeting complex promotes clearance of misfolded prohormones from the endoplasmic reticulum (ER) for lysosomal destruction by ER-phagy. Because RTN3 resides in the cytosolic leaflet of the ER bilayer, the mechanism of selecting misfolded prohormones as ER-phagy cargo on the luminal side of the ER membrane remains unknown. Here we identify the ER transmembrane protein PGRMC1 as an RTN3-binding partner. Via its luminal domain, PGRMC1 captures misfolded prohormones, targeting them for RTN3-dependent ER-phagy. PGRMC1 selects cargos that are smaller than the large size of other reported ER-phagy substrates. Cargos for PGRMC1 include mutant proinsulins that block secretion of wildtype proinsulin through dominant-negative interactions within the ER, causing insulin-"],"journal":["Nature communications"],"pubmed_title":["PGRMC1 acts as a size-selective cargo receptor to drive ER-phagic clearance of mutant prohormones."],"pmcid":["PMC8514460"],"funding_grant_id":["P30 DK020572","T32 GM007315","F31 DK128868","R01 DK048280","R01 DK111174"],"pubmed_authors":["Haataja L","Tsai B","Knupp J","Chen YJ","Arvan P","Arunagiri A"],"additional_accession":[]},"is_claimable":false,"name":"PGRMC1 acts as a size-selective cargo receptor to drive ER-phagic clearance of mutant prohormones.","description":"The reticulon-3 (RTN3)-driven targeting complex promotes clearance of misfolded prohormones from the endoplasmic reticulum (ER) for lysosomal destruction by ER-phagy. Because RTN3 resides in the cytosolic leaflet of the ER bilayer, the mechanism of selecting misfolded prohormones as ER-phagy cargo on the luminal side of the ER membrane remains unknown. Here we identify the ER transmembrane protein PGRMC1 as an RTN3-binding partner. Via its luminal domain, PGRMC1 captures misfolded prohormones, targeting them for RTN3-dependent ER-phagy. PGRMC1 selects cargos that are smaller than the large size of other reported ER-phagy substrates. Cargos for PGRMC1 include mutant proinsulins that block secretion of wildtype proinsulin through dominant-negative interactions within the ER, causing insulin-","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Oct","modification":"2026-05-08T17:12:31.21Z","creation":"2022-02-11T12:22:26.895Z"},"accession":"S-EPMC8514460","cross_references":{"pubmed":["34645803"],"doi":["10.1038/s41467-021-26225-8"]}}