The Endocytic Adaptor Eps15 Controls Marginal Zone B Cell Numbers

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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Main Authors: Pozzi, Benedetta, Amodio, Stefania, Lucano, Caterina, Sciullo, Anna, Ronzoni, Simona, Castelletti, Daniela, Adler, Thure, Treise, Irina, Betsholtz, Ingrid Holmberg, Rathkolb, Birgit, Busch, Dirk H., Wolf, Eckhard, Fuchs, Helmut, Gailus-Durner, Valérie, de Angelis, Martin Hrabě, Betsholtz, Christer, Casola, Stefano, Di Fiore, Pier Paolo, Offenhäuser, Nina
Format: Online
Language:English
Published: Public Library of Science 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511280/
id pubmed-3511280
recordtype oai_dc
spelling pubmed-35112802012-12-05 The Endocytic Adaptor Eps15 Controls Marginal Zone B Cell Numbers Pozzi, Benedetta Amodio, Stefania Lucano, Caterina Sciullo, Anna Ronzoni, Simona Castelletti, Daniela Adler, Thure Treise, Irina Betsholtz, Ingrid Holmberg Rathkolb, Birgit Busch, Dirk H. Wolf, Eckhard Fuchs, Helmut Gailus-Durner, Valérie de Angelis, Martin Hrabě Betsholtz, Christer Casola, Stefano Di Fiore, Pier Paolo Offenhäuser, Nina Research Article 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. Public Library of Science 2012-11-30 /pmc/articles/PMC3511280/ /pubmed/23226392 http://dx.doi.org/10.1371/journal.pone.0050818 Text en © 2012 Pozzi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Pozzi, Benedetta
Amodio, Stefania
Lucano, Caterina
Sciullo, Anna
Ronzoni, Simona
Castelletti, Daniela
Adler, Thure
Treise, Irina
Betsholtz, Ingrid Holmberg
Rathkolb, Birgit
Busch, Dirk H.
Wolf, Eckhard
Fuchs, Helmut
Gailus-Durner, Valérie
de Angelis, Martin Hrabě
Betsholtz, Christer
Casola, Stefano
Di Fiore, Pier Paolo
Offenhäuser, Nina
spellingShingle Pozzi, Benedetta
Amodio, Stefania
Lucano, Caterina
Sciullo, Anna
Ronzoni, Simona
Castelletti, Daniela
Adler, Thure
Treise, Irina
Betsholtz, Ingrid Holmberg
Rathkolb, Birgit
Busch, Dirk H.
Wolf, Eckhard
Fuchs, Helmut
Gailus-Durner, Valérie
de Angelis, Martin Hrabě
Betsholtz, Christer
Casola, Stefano
Di Fiore, Pier Paolo
Offenhäuser, Nina
The Endocytic Adaptor Eps15 Controls Marginal Zone B Cell Numbers
author_facet Pozzi, Benedetta
Amodio, Stefania
Lucano, Caterina
Sciullo, Anna
Ronzoni, Simona
Castelletti, Daniela
Adler, Thure
Treise, Irina
Betsholtz, Ingrid Holmberg
Rathkolb, Birgit
Busch, Dirk H.
Wolf, Eckhard
Fuchs, Helmut
Gailus-Durner, Valérie
de Angelis, Martin Hrabě
Betsholtz, Christer
Casola, Stefano
Di Fiore, Pier Paolo
Offenhäuser, Nina
author_sort Pozzi, Benedetta
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
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.
publisher Public Library of Science
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511280/
_version_ 1611936927957647360

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