Journal article
Recruitment of Cbl-b to B cell antigen receptor couples antigen recognition to Toll-like receptor 9 activation in late endosomes
PloS one, Vol.9(3), pp.e89792-e89792
2014
DOI: 10.1371/journal.pone.0089792
PMCID: PMC3961229
PMID: 24651487
Abstract
Casitas B-lineage lymphoma-b (Cbl-b) is a ubiquitin ligase (E3) that modulates signaling by tagging molecules for degradation. It is a complex protein with multiple domains and binding partners that are not involved in ubiquitinating substrates. Herein, we demonstrate that Cbl-b, but not c-Cbl, is recruited to the clustered B cell antigen receptor (BCR) and that Cbl-b is required for entry of endocytosed BCRs into late endosomes. The E3 activity of Cbl-b is not necessary for BCR endocytic trafficking. Rather, the ubiquitin associated (UBA) domain is required. Furthermore, the Cbl-b UBA domain is sufficient to confer the receptor trafficking functions of Cbl-b on c-Cbl. Cbl-b is also required for entry of the Toll-like receptor 9 (TLR9) into late endosomes and for the in vitro activation of TLR9 by BCR-captured ligands. These data indicate that Cbl-b acts as a scaffolding molecule to coordinate the delivery of the BCR and TLR9 into subcellular compartments required for productively delivering BCR-captured ligands to TLR9.
Details
- Title: Subtitle
- Recruitment of Cbl-b to B cell antigen receptor couples antigen recognition to Toll-like receptor 9 activation in late endosomes
- Creators
- Margaret Veselits - Section of Rheumatology, Department of Medicine and Knapp Center for Lupus and Immunological Research, University of Chicago, Chicago, Illinois, United States of AmericaAzusa Tanaka - Section of Rheumatology, Department of Medicine and Knapp Center for Lupus and Immunological Research, University of Chicago, Chicago, Illinois, United States of AmericaStanley Lipkowitz - Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of AmericaShannon O'Neill - Integrated Department of Immunology, National Jewish Medical and Research Center and University of Colorado and Health Sciences Center, Denver, Colorado, United States of AmericaRoger Sciammas - Section of Rheumatology, Department of Medicine and Knapp Center for Lupus and Immunological Research, University of Chicago, Chicago, Illinois, United States of AmericaAlison Finnegan - Department of Immunology and Microbiology, and Department of Internal Medicine, Section of Rheumatology, Rush University Medical Center, Chicago, Illinois, United States of AmericaJian Zhang - Section of Nephrology, Department of Medicine, University of Chicago, Chicago, Illinois, United States of AmericaMarcus R Clark - Section of Rheumatology, Department of Medicine and Knapp Center for Lupus and Immunological Research, University of Chicago, Chicago, Illinois, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.9(3), pp.e89792-e89792
- DOI
- 10.1371/journal.pone.0089792
- PMID
- 24651487
- PMCID
- PMC3961229
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science; United States
- Grant note
- GM088847 / NIGMS NIH HHS Intramural NIH HHS R01 GM101090 / NIGMS NIH HHS AI090901 / NIAID NIH HHS R21 GM076601 / NIGMS NIH HHS R01 GM067772 / NIGMS NIH HHS R01 AI090901 / NIAID NIH HHS R01 GM088847 / NIGMS NIH HHS GM101090 / NIGMS NIH HHS
- Language
- English
- Date published
- 2014
- Academic Unit
- Pathology
- Record Identifier
- 9984047706602771
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