The endocytic adaptor Eps15 controls marginal zone B cell numbers.
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 mammal...
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doaj-31ca96846b3a447d81e1e9a7762f27472020-11-25T01:31:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e5081810.1371/journal.pone.0050818The endocytic adaptor Eps15 controls marginal zone B cell numbers.Benedetta PozziStefania AmodioCaterina LucanoAnna SciulloSimona RonzoniDaniela CastellettiThure AdlerIrina TreiseIngrid Holmberg BetsholtzBirgit RathkolbDirk H BuschEckhard WolfHelmut FuchsValérie Gailus-DurnerMartin Hrabě de AngelisChrister BetsholtzStefano CasolaPier Paolo Di FioreNina OffenhäuserEps15 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.http://europepmc.org/articles/PMC3511280?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Benedetta Pozzi Stefania Amodio Caterina Lucano Anna Sciullo Simona Ronzoni Daniela Castelletti Thure Adler Irina Treise Ingrid Holmberg Betsholtz Birgit Rathkolb Dirk H Busch Eckhard Wolf Helmut Fuchs Valérie Gailus-Durner Martin Hrabě de Angelis Christer Betsholtz Stefano Casola Pier Paolo Di Fiore Nina Offenhäuser |
spellingShingle |
Benedetta Pozzi Stefania Amodio Caterina Lucano Anna Sciullo Simona Ronzoni Daniela Castelletti Thure Adler Irina Treise Ingrid Holmberg Betsholtz Birgit Rathkolb Dirk H Busch Eckhard Wolf Helmut Fuchs Valérie Gailus-Durner Martin Hrabě de Angelis Christer Betsholtz Stefano Casola Pier Paolo Di Fiore Nina Offenhäuser The endocytic adaptor Eps15 controls marginal zone B cell numbers. PLoS ONE |
author_facet |
Benedetta Pozzi Stefania Amodio Caterina Lucano Anna Sciullo Simona Ronzoni Daniela Castelletti Thure Adler Irina Treise Ingrid Holmberg Betsholtz Birgit Rathkolb Dirk H Busch Eckhard Wolf Helmut Fuchs Valérie Gailus-Durner Martin Hrabě de Angelis Christer Betsholtz Stefano Casola Pier Paolo Di Fiore Nina Offenhäuser |
author_sort |
Benedetta Pozzi |
title |
The endocytic adaptor Eps15 controls marginal zone B cell numbers. |
title_short |
The endocytic adaptor Eps15 controls marginal zone B cell numbers. |
title_full |
The endocytic adaptor Eps15 controls marginal zone B cell numbers. |
title_fullStr |
The endocytic adaptor Eps15 controls marginal zone B cell numbers. |
title_full_unstemmed |
The endocytic adaptor Eps15 controls marginal zone B cell numbers. |
title_sort |
endocytic adaptor eps15 controls marginal zone b cell numbers. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3511280?pdf=render |
work_keys_str_mv |
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