Fig. 1

The pathway of ecto-F1-ATPase-mediated holo-HDL endocytosis. (1) ApoA-I, found on the HDL molecule, binds to the beta-subunit of the ecto-F1-ATPase of a hepatocyte; (2) This binding activates ecto-F1-ATPase, causing it to increase the production of ADP from ATP; (3) With the extracellular concentration of ADP increased, P2Y₁₃, a G protein-coupled receptor, is activated, phosphorylating the GDP molecule found on the alpha-subunit of the G Protein. This phosphorylation activates the G protein, releasing it from its beta and gamma subunits; (4) The G Protein then activates RhoA by phosphorylation, causing the G Protein to become inactive where it will return to join its beta and gamma subunits on the inner plasma membrane. Activated RhoA will then donate a phosphate group to ROCK1, activating the protein; (5) ROCK1 then drives the cytoskeletal modifications necessary for holo-HDL endocytosis