Fig. 7.

Schematic representation of a working model for endosomal transport involving CLC-5 and KIF3B interaction in polarized cells. CLC-5 and KIF3B are expressed in polarized renal proximal tubular cells which reabsorb proteins and solutes via the receptor-mediated endocytic pathway that uses megalin and cubilin as the apical plasma membrane (APM) receptors (4, 7, 17). Ligands bind to these receptors at the APM where CLC-5 and interacting proteins Nedd4-2, NHERF2, and cofilin are also present (23, 24, 26). The receptor-ligand complex is internalized in vesicles, containing CLC-5 and CLC-4 (40), which are anterogradely transported along microtubules via the Kinesin-2 complex (17). These vesicles fuse with early endosomes where acidification involves the vacuolar H⁺-ATPase, with counter ions being provided by CLC-5 (28). In nonpolarized cells, the orientation of the microtubules is reversed (Fig. 3F), and CLC-5 vesicles would be transported to the cell surface.