RT Journal Article SR Electronic T1 Redundant and nonredundant organismal functions of EPS15 and EPS15L1 JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201800273 DO 10.26508/lsa.201800273 VO 2 IS 1 A1 Milesi, Cinzia A1 Alberici, Paola A1 Pozzi, Benedetta A1 Oldani, Amanda A1 Beznoussenko, Galina V A1 Raimondi, Andrea A1 Soppo, Blanche Ekalle A1 Amodio, Stefania A1 Caldieri, Giusi A1 Malabarba, Maria Grazia A1 Bertalot, Giovanni A1 Confalonieri, Stefano A1 Parazzoli, Dario A1 Mironov, Alexander A A1 Tacchetti, Carlo A1 Di Fiore, Pier Paolo A1 Sigismund, Sara A1 Offenhäuser, Nina YR 2019 UL http://www.life-science-alliance.org/content/2/1/e201800273.abstract AB 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.