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Publication : Redundant and nonredundant organismal functions of EPS15 and EPS15L1.

First Author  Milesi C Year  2019
Journal  Life Sci Alliance Volume  2
Issue  1 PubMed ID  30692166
Mgi Jnum  J:272122 Mgi Id  MGI:6283940
Doi  10.26508/lsa.201800273 Citation  Milesi C, et al. (2019) Redundant and nonredundant organismal functions of EPS15 and EPS15L1. Life Sci Alliance 2(1)
abstractText  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.
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