Clathrin functions in intracellular sorting during receptor‐mediated endocytosis

Clathrin is a key protein involved in receptor-mediated endocytosis (RME), which is also known as clathrin-mediated endocytosis (CME). Ligand/receptor binding facilitates clathrin clustering and cell surface invagination. We recently found that the typical CME ligand transferrin (Tf) can be internalized into cells without the clathrin heavy chain (CLTC). In this study, we clarified the unknown roles of clathrin during intracellular trafficking. Microscopic observation revealed that Tf accumulates in the deeper compartments of CLTC-knockdown HeLa cells. A colocalization analysis with endosome/lysosome markers showed that endocytosed Tf moves to early/late endosomes and then to lysosomes in CLTC-knockdown cells. This suggests that clathrin contributes to the recycling and exocytosis of endocytosed molecules.