Recycling endosomal CD133 functions as an inhibitor of autophagy at the pericentrosomal region.

CD133 is a transmembranous protein that mainly localises to the plasma membrane in haematopoietic and neural stem cells as well as cancer stem cells. Although CD133 also localises to the cytoplasm, the mechanism of action and function of cytoplasmic CD133 currently remain unknown. We herein demonstrated that when Src family kinase activity is weak, CD133 interacts with HDAC6 and is transported to the pericentrosomal region after internalization and endosome formation via the dynein-based traffic system. Pericentrosomal CD133 is then recycled to the plasma membrane via recycling endosomes. At the pericentrosomal region, endosomal CD133 captures GABARAP, an initiator of autophagy, and inhibits GABARAP-mediated ULK1 activation and the subsequent initiation of autophagy. Furthermore, pericentrosomal CD133 suppresses cell differentiation, such as primary cilium formation and neurite outgrowth, by inhibiting autophagy. Thus, the present results provide evidence to suggest that pericentrosomal CD133 has the unique property of maintaining the undifferentiated status of cells by inhibiting autophagy.