The ER transmembrane protein PGRMC1 recruits misfolded proteins for reticulophagic clearance

ER-phagy: mechanisms, regulation, and diseases connected to the lysosomal clearance of the endoplasmic reticulum

“…The case of RTN3L merits a note. The concomitant silencing of all the RTN3 isoforms results in the accumulation of ER-to-lysosome-associated degradation clients, such as the protein condensates and complexes formed in the ER lumen by proinsulin Akita, the C28F mutant of proopiomelanocortin, and the G57S variant of the neuropeptide pro-arginine-vasopressin ( 440 , 456 , 457 ). The finding that the ER-to-lysosome-associated degradation defect caused by the depletion of RTN3 proteins is rescued upon backtransfection of either the short form of RTN3 or RTN4, both of which lack LIR motifs, warrants further investigation ( 440 ).…”

Progesterone receptor membrane component 1 facilitates Ca2+ signal amplification between endosomes and the endoplasmic reticulum

“…Such roles include endocytic trafficking ( 32 , 33 , 34 ), insulin homeostasis ( 35 , 36 ), lipid homeostasis ( 34 , 37 ), as well as axonal guidance and synaptogenesis ( 14 ). PGRMC1 is also implicated in various pathophysiological outcomes such as non-alcoholic fatty liver disease ( 38 ), diabetes ( 39 ) and cancer ( 22 , 29 , 40 , 41 ), which parallel the emerging role of the TPC complex in many of the same disease states ( 5 , 7 , 8 ). We note PGRMC1 is highly expressed in several cancer types, serving to accelerate tumor progression and being associated with poor clinical prognosis.…”

Adaptive responses of neuronal cells to chronic endoplasmic reticulum (ER) stress

“…In addition, changes in expression of RTN3L and ATL3 imply that an effective turnover of ER tubules and tubule junctions plays an important role in the adaptation to chronic ER stress. Indeed, RTN3L drives degradation of protein aggregates in the ER lumen [ [61] , [62] , [63] ].…”