Fig. 3

CD133 impacts the architecture of actin-based microvilli and microtubule-based primary cilia. a, b CD133 is involved in the architecture of microvilli (a) and primary cilia (b), two distinct types of membrane protrusions based on actin filaments and microtubules, respectively. In microvilli, mutation (2 M) in the GM₁-binding domain of CD133 creates branched microvilli and/or microvilli with a knob-like structure, while the mutation of tyrosine 828 by phenylalanine (2 M Y828F or Y828F mutants; numbered according to CD133.s2) abolishes these phenotypes and creates short microvilli (a, left panel). Branching of the microvilli results from the interaction of phosphorylated CD133 with the Arp2/3 complex, whereas the interaction with PI3K, which stimulates the conversion of PIP₂ to PIP₃ in the inner leaflet of the plasma membrane, uncouples the plasma membrane and the underlying cytoskeleton, resulting in irregularly shaped microvilli (a, right panel). Both subunits (p85 and p110) of PI3K and all seven subunits of the Arp2/3 complex are represented. In primary cilium, overexpression of CD133 increased cilium length, while K138Q mutation led to the formation of short cilia and the appearance of EVs derived therefrom (b, left panel). The dual interaction of CD133, mediated by K138, with Arl13b and HDAC6 regulate the assembly and disassembly, respectively, of the ciliary structure. Arl13b binding to CD133 also depends on tyrosine 828 phosphorylation (b, right panel). Ac, acetylated tubulin. c CD133 plays an essential role in the recruitment of molecular regulators (Arl13b and HDAC6) controlling the dynamics of the ciliary compartment during the activation of quiescent stem cells into transit amplifying cells, as demonstrated in incisor tooth epithelial cells—a process impaired in CD133-null mice. Illustrations in a–c are based on data presented in Refs [177, 182, 183]