Pericentrosomal redistribution of the endoplasmic reticulum ensures organelle symmetric inheritance and mitotic progression

Symmetric cell division entails the equal distribution of cellular components to daughter cells. However, the mechanisms governing organelle segregation remain elusive. The endoplasmic reticulum (ER), comprising pericentrosomal sheets and peripheral tubules in interphase, serves as a central hub for sensing cellular states and coordinating other organelle dynamics. Dysregulation of ER morphology and distribution is implicated in developmental disorders and tumorigenesis. Here, we show that upon mitotic entry, the ER undergoes reverse redistribution: tubular ER accumulates around the centrosomes, while sheet-like ER relocates to the periphery. Mechanistically, the tubular ER protein RTN4 is phosphorylated by CDK1 and translocated toward centrosomes in a dynein-dependent manner by binding to Rab11 GTPase, thereby promoting tubularization of the pericentrosomal ER. RTN4-mediated ER reorganization ensures symmetric distribution and inheritance of the ER, further contributing to the symmetric segregation of other organelles and proper mitotic progression. In Caenorhabditis elegans, the RTN4 homolog RET-1 also drives pericentrosomal ER enrichment during embryonic cell division and facilitates development. Thus, our study uncovers the mechanism of mitotic ER symmetry remodeling and its roles in organelle inheritance, mitotic progression, and development.