Fig. 2.

Absorption and intra-cellular handling of LMW proteins in the proximal tubule. Megalin is present on the cell surface in high abundance. When low-molecular-weight proteins bind to megalin, this “cargo” is internalized into the early endosome. The endosome is acidified by the action of H⁺ATPase in concert with chloride channel 5 (CLCN5). At low pH, the cargo dissociates from megalin and passes through the late endosome and on to the lysosome where it is degraded. Megalin returns from the early endosome back to the surface of the cell, where it is available for internalization of more cargo. From Guggino [16], reproduced with permission