TY - JOUR
T1 - The Endocytic Adaptor Eps15 Controls Marginal Zone B Cell Numbers
AU - Pozzi, Benedetta
AU - Amodio, Stefania
AU - Lucano, Caterina
AU - Sciullo, Anna
AU - Ronzoni, Simona
AU - Castelletti, Daniela
AU - Adler, Thure
AU - Treise, Irina
AU - Betsholtz, Ingrid Holmberg
AU - Rathkolb, Birgit
AU - Busch, Dirk H.
AU - Wolf, Eckhard
AU - Fuchs, Helmut
AU - Gailus-Durner, Valérie
AU - de Angelis, Martin Hrabě
AU - Betsholtz, Christer
AU - Casola, Stefano
AU - Di Fiore, Pier Paolo
AU - Offenhäuser, Nina
PY - 2012/11/30
Y1 - 2012/11/30
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0050818
DO - 10.1371/journal.pone.0050818
M3 - Article
C2 - 23226392
AN - SCOPUS:84870705019
VL - 7
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 11
M1 - e50818
ER -