Fig. 6

Tunneling nanotubes mediate the transfer of CD133 between hematopoietic stem and progenitor cells. CD133 is exchanged between CD133⁺CD34⁺HSPCs (or KG1a hematopoietic leukemic cells) via TNTs. In various cellular systems, these transient narrow actin-based tubular connections have been reported to mediate the transfer of organelles, soluble and membrane proteins and nucleic acids or to contribute to calcium signaling, thereby promoting intercellular communication between adjacent or distant cells. In cells of hematopoietic origin, TNT biogenesis depends on cell polarization and occurs during cell migration (solid arrow) with one of two cells in direct contact forming membrane extensions from the uropod membrane at its rear pole, where CD133 is concentrated. Mechanistically, the biological properties of CD133, including its direct interaction with membrane cholesterol (red lipid) and its incorporation into cholesterol-rich membrane microdomains, may modulate the lipid composition and the local organization of the plasma membrane in TNTs. The CD133 interaction with PI3K may lead to the conversion of the docking PIP₂ into PIP₃ at the inner leaflet of CD133-containing membrane microdomains, thereby regulating their interaction with the underlying actin cytoskeleton. The binding of the actin motor protein myosin to PIP₃ clusters may promote the selective movement of such CD133-containing membrane microdomains along the actin filament and mediate their transfer between TNT-connected cells (dashed arrow). Illustration is adapted from Ref [308]