@article {Milesie201800273, author = {Cinzia Milesi and Paola Alberici and Benedetta Pozzi and Amanda Oldani and Galina V Beznoussenko and Andrea Raimondi and Blanche Ekalle Soppo and Stefania Amodio and Giusi Caldieri and Maria Grazia Malabarba and Giovanni Bertalot and Stefano Confalonieri and Dario Parazzoli and Alexander A Mironov and Carlo Tacchetti and Pier Paolo Di Fiore and Sara Sigismund and Nina Offenh{\"a}user}, title = {Redundant and nonredundant organismal functions of EPS15 and EPS15L1}, volume = {2}, number = {1}, elocation-id = {e201800273}, year = {2019}, doi = {10.26508/lsa.201800273}, publisher = {Life Science Alliance}, abstract = {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.}, URL = {https://www.life-science-alliance.org/content/2/1/e201800273}, eprint = {https://www.life-science-alliance.org/content/2/1/e201800273.full.pdf}, journal = {Life Science Alliance} }