TY - JOUR T1 - Redundant and nonredundant organismal functions of EPS15 and EPS15L1 JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201800273 VL - 2 IS - 1 SP - e201800273 AU - Cinzia Milesi AU - Paola Alberici AU - Benedetta Pozzi AU - Amanda Oldani AU - Galina V Beznoussenko AU - Andrea Raimondi AU - Blanche Ekalle Soppo AU - Stefania Amodio AU - Giusi Caldieri AU - Maria Grazia Malabarba AU - Giovanni Bertalot AU - Stefano Confalonieri AU - Dario Parazzoli AU - Alexander A Mironov AU - Carlo Tacchetti AU - Pier Paolo Di Fiore AU - Sara Sigismund AU - Nina Offenhäuser Y1 - 2019/02/01 UR - https://www.life-science-alliance.org/content/2/1/e201800273.abstract N2 - EPS15 and its homologous EPS15L1 are endocytic accessory proteins. Studies in mammalian cell lines suggested that EPS15 and EPS15L1 regulate endocytosis in a redundant manner. However, at the organismal level, it is not known to which extent the functions of the two proteins overlap. Here, by exploiting various constitutive and conditional null mice, we report redundant and nonredundant functions of the two proteins. EPS15L1 displays a unique nonredundant role in the nervous system, whereas both proteins are fundamental during embryo development as shown by the embryonic lethality of -Eps15/Eps15L1-double KO mice. At the cellular level, the major process redundantly regulated by EPS15 and EPS15L1 is the endocytosis of the transferrin receptor, a pathway that sustains the development of red blood cells and controls iron homeostasis. Consequently, hematopoietic-specific conditional Eps15/Eps15L1-double KO mice display traits of microcytic hypochromic anemia, due to a cell-autonomous defect in iron internalization. ER -