Differential dopamine receptor subtype regulation of adenylyl cyclases in lipid rafts in human embryonic kidney and renal proximal tubule cells

In HEK-293 cells, lipid rafts contain D1R, D5R, and flotillin-1, but not caveolin-1, and keep adenylyl cylase (AC) in the active state. In contrast, lipid rafts in human renal proximal tubule (hRPT) cells contain D1R, D5R, and caveolin-1, and keep the AC in the inactive state. In hRPT cells, cholesterol depletion disrupts the lipid rafts and causes the movement of AC to non-lipid rafts, resulting in increased signaling efficacy (cAMP production). However, the AC remains in the lipid rafts, while the receptors move to non-lipid rafts, with disruption of lipid rafts in HEK-293 cells. This segregation of receptors and signaling molecules into different compartments leads to a decrease in the signal transduction.113