PT  - JOURNAL ARTICLE
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
TI  - Redundant and nonredundant organismal functions of EPS15 and EPS15L1
AID  - 10.26508/lsa.201800273
DP  - 2019 Feb 01
TA  - Life Science Alliance
PG  - e201800273
VI  - 2
IP  - 1
4099  - https://www.life-science-alliance.org/content/2/1/e201800273.short
4100  - https://www.life-science-alliance.org/content/2/1/e201800273.full
SO  - Life Sci. Alliance2019 Feb 01; 2
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.