Cholesterol Trafficking in CaCo-2 Cells

Abstract

In CaCo-2 cells, the transport of cholesterol from the plasma membrane to the endoplasmic reticulum occurs via transport vesicles, likely derived from specialized domains of the plasma membrane. Agents that inhibit p-glycoprotein activity interfere with the transport of plasma membrane cholesterol to the endoplasmic reticulum and the secretion of triacylglycerol-rich lipoproteins. The uptake of micellar cholesterol causes the “clustering” of plasma membrane cholesterol to specialized microdomains of the plasma membrane containing caveolin. It is likely that it is from these areas that plasma membrane cholesterol fluxes to the endoplasmic reticulum. Cholesterol derived from the plasma membrane is the major substrate for ACAT and triacylglycerol-rich lipoprotein cholesterol. The transport of newly-synthesized cholesterol from the endoplasmic reticulum to the plasma membrane is constitutive and independent of Golgi, microtubular function, new protein synthesis, or p-glycoprotein. CaCo-2 cells regulate the amount of newly-synthesized cholesterol arriving at the plasma membrane by altering the rate of cholesterol synthesis, not by altering the transport process. The pathways that transport cholesterol to and from the plasma membrane are distinct.