In: PLOS ONE
8(5)
[PDF, 2MB]
Abstract
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. We generated Eps15-KO mice to investigate its function in mammals. Eps15-KO mice are born at the expected Mendelian ratio and are fertile. Using a large-scale phenotype screen covering more than 300 parameters correlated to human disease, we found that Eps15-KO mice did not show any sign of disease or neural deficits. Instead, altered blood parameters pointed to an immunological defect. By competitive bone marrow transplantation we demonstrated that Eps15-KO hematopoietic precursor cells were more efficient than the WT counterparts in repopulating B220⁺ bone marrow cells, CD19⁻ thymocytes and splenic marginal zone (MZ) B cells. Eps15-KO mice showed a 2-fold increase in MZ B cell numbers when compared with controls. Using reverse bone marrow transplantation, we found that Eps15 regulates MZ B cell numbers in a cell autonomous manner. FACS analysis showed that although MZ B cells were increased in Eps15-KO mice, transitional and pre-MZ B cell numbers were unaffected. The increase in MZ B cell numbers in Eps15 KO mice was not dependent on altered BCR signaling or Notch activity. In conclusion, in mammals, the endocytic adaptor protein Eps15 is a regulator of B-cell lymphopoiesis.
Dokumententyp: | Zeitschriftenartikel |
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Publikationsform: | Publisher's Version |
Fakultät: | Tiermedizin |
Themengebiete: | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften; Biologie |
URN: | urn:nbn:de:bvb:19-epub-15681-1 |
ISSN: | 1932-6203 |
Sprache: | Englisch |
Dokumenten ID: | 15681 |
Datum der Veröffentlichung auf Open Access LMU: | 21. Jun. 2013, 12:51 |
Letzte Änderungen: | 04. Nov. 2020, 12:56 |