Asymmetric Pericentrosomal CD133 Endosomes Induce the Unequal Autophagic Activity During Cytokinesis in CD133-Positive Human Neuroblastoma Cells

CD133 is a transmembrane protein that mainly localizes to the plasma membrane in hematopoietic/neural stem cells and cancer stem cells. Although CD133 also localizes to the cytoplasm and is degraded through autophagy, the precise mechanisms responsible for the autophagic degradation of endosomal CD133 currently remain unknown. We demonstrated that endosomal CD133 has unique properties for cell homeostasis. Endosomal CD133 is degraded through p62/SQSTM1-mediated selective autophagy. However, in low basal autophagic cells, such as SK-N-DZ and SH-SY5Y cells, endosomal CD133 accumulates at the pericentrosomal region and conversely suppresses autophagy. Endosomal CD133 also asymmetrically distributes to the pericentrosomal region and induces unequal autophagic activity between 2 daughter cells during cytokinesis in SK-N-DZ and TGW cells. In addition, the asymmetric distribution of pericentrosomal CD133 endosomes and nuclear beta-catenin cooperatively suppresses autophagic activity against p62 in SK-N-DZ cells. Thus, the present study suggests that the asymmetric distribution of pericentrosomal CD133 endosomes induces the symmetry breaking of autophagic activity during cytokinesis in cooperation with nuclear beta-catenin.

Automated summary

CD133 is a transmembrane protein mainly located on the plasma membrane of stem cells and cancer stem cells. The study demonstrates that CD133 plays a significant role in cell homeostasis by being degraded through selective autophagy and regulating autophagic activity. The asymmetric distribution of CD133 and nuclear beta-catenin during cell division induces a symmetry breaking of autophagic activity.