Fig. 4

The impact of CD133 on autophagy relies on its phosphorylation status. a Under severe growth conditions, the absence of Src-dependent phosphorylation of CD133 Y828 favors its internalization into recycling endosomes. Through its interaction with HDAC6, CD133 is redistributed via motor protein dynein and microtubules to the pericentrosomal region, where its binding to GABARAP prevents autophagy by hindering the GABARAP interaction with ULK1. Suppression of perinuclear CD133-mediated autophagy in cells with stem cell properties favors the maintenance of an undifferentiated state. b The asymmetric distribution of CD133 in dividing neuroblastoma cells impacts autophagic activity in nascent cells. During cytokinesis, the presence of CD133 together with GABARAP and HDAC6 in recycling endosomes located asymmetrically in the pericentrosomal region and the nuclear translocation of β-catenin cooperatively suppress the autophagic activity in a nascent daughter cell by inhibiting GABARAP-mediated initiation of autophagy and repressing the expression of SQSTM1, which may also protect CD133 from degradation. Such interplay may promote the maintenance of stem characteristics via a reduction in autophagy, while the absence of CD133 and increased autophagy may favor cell differentiation. Illustrations in panels a and b are adapted from Refs [190] and [247], respectively