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Eps15 – a regulator of B-cell lymphopoeisis

Eps15 is an endocytic adaptor protein involved in clathrin and non-clathrin mediated endocytosis. In Caenorhabditis elegans and Drosophila melanogaster lack of Eps15 leads to defects in synaptic vesicle recycling and synapse formation (synapse formation only in Drosophila). The scientists around Benedetta Pozzi from the IFOM Fondazione Instituto FIRC di Oncologica Moleculare in Milan, Italy, analysed Eps15-knockout mice to investigate its function in mammals. The knockout war generated by Crister Betsholtz at the Karolinska Institute, Sweden. Eps15-KO mice are born at the expected Mendelian ratio and are fertile. In the GMC large-scale phenotype screen it turned out that Eps15-KO mice did not show any sign of disease or neural deficits. Instead, altered blood parameters pointed to an immunological defect. The percentage of lymphocytes was reduced whereas the number of other blood cells was comparable to control animals.
In further experiments – competitive bone marrow transplantation and reverse bone marrow transplantation – it could be shown that Eps15 is involved in the regulation of lymphocyte homeostasis, most notably in the marginal zone (MZ) B cell population. This mechanism is independent of Notch and BCR signalling which are known to play a key role in the regulation of MZ B cell development.

The Endocytic Adaptor Eps15 Controls Marginal Zone B Cell Numbers, Pozzi et al., 2012, PLOS ONE, Vol 7 (11), e50818