SGIP1α is an endocytic protein that directly interacts with phospholipids and Eps15

SGIP1 has been shown to be an endophilin-interacting protein that regulates energy balance, but its function is not fully understood. Here, we identified its splicing variant of SGIP1 and named it SGIP1 alpha. SGIP1 alpha bound to phosphatidylserine and phosphoinositides and deformed the plasma membrane and liposomes into narrow tubules, suggesting the involvement in vesicle formation during endocytosis. SGIP1 alpha furthermore bound to Eps15, an important adaptor protein of clathrin-mediated endocytic machinery. SGIP1 alpha was colocalized with Eps15 and the AP-2 complex. Upon epidermal growth factor (EGF) stimulation, SGIP1 alpha was colocalized with EGF at the plasma membrane, indicating the localization of SGIP1 alpha at clathrin-coated pits/vesicles. SGIP1 alpha overexpression reduced transferrin and EGF endocytosis. SGIP1 alpha knockdown reduced transferrin endocytosis but not EGF endocytosis; this difference may be due to the presence of redundant pathways in EGF endocytosis. These results suggest that SGIP1 alpha plays an essential role in clathrin-mediated endocytosis by interacting with phospholipids and Eps15.