The assembly of RAB22A/TMEM33/RTN4 initiates a secretory ER-phagy pathway.

ABSTRACT: Rafeesome, a newly identified multivesicular body (MVB)-like organelle, forms through the fusion of RAB22A-mediated ER-derived noncanonical autophagosomes with RAB22A-positive early endosomes. However, the mechanism underlying the formation of RAB22A-mediated noncanonical autophagosomes remains unclear. Herein, we report a secretory ER-phagy pathway in which the assembly of RAB22A/TMEM33/RTN4 induces the clustering of high-molecular-weight RTN4 oligomers, leading to ER membrane remodeling. This remodeling drives the biogenesis of ER-derived RTN4-positive noncanonical autophagosomes, which are ultimately secreted as TMEM33-marked RAB22A-induced extracellular vesicles (R-EVs) via Rafeesome. Specifically, RAB22A interacts with the tubular ER membrane protein TMEM33, which binds to the TM2 dom

SUBMITTER: Zheng X 

PROVIDER: S-EPMC12041605 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature