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.