Annexin VI stimulates endocytosis and is involved in the trafficking of low density lipoprotein to the prelysosomal compartment

Annexins are calcium-binding proteins with a wide distribution in most pola rized and nonpolarized cells that participate in a variety of membrane-memb rane interactions. At the cell surface, annexin VI is thought to remodel th e spectrin cytoskeleton to facilitate budding of coated pits. However, anne xin VI is also found in late endocytic compartments in a number of cell typ es, indicating an additional important role at later stages of the endocyti c pathway. Therefore overexpression of annexin VI in Chinese hamster ovary cells was used to investigate its possible role in endocytosis and intracel lular trafficking of low density Lipoprotein (LDL) and transferrin, While o verexpression of annexin VI alone did not alter endocytosis and degradation of LDL, coexpression of annexin VI and LDL receptor resulted in an increas e in LDL uptake with a concomitant increase of its degradation. Whereas ann exin VI showed a wide intracellular distribution in resting Chinese hamster ovary cells, it was mainly found in the endocytic compartment and remained associated with LDE-containing vesicles even at later stages of the endocy tic pathway. Thus, data presented in this study suggest that after stimulat ing endocytosis at the cell surface, annexin VI remains hound to endocytic vesicles to regulate entry of ligands into the prelysosomal compartment.