Recruitment of Cbl-b to B Cell Antigen Receptor Couples Antigen Recognition to Toll-like Receptor 9 Activation in Late Endosomes

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Mar 22

PMID 24651487

Citations 8

Authors

Margaret Veselits

Azusa Tanaka

Stanley Lipkowitz

Shannon ONeill

Roger Sciammas

Alison Finnegan

Jian Zhang

Marcus R Clark

Affiliations

Soon will be listed here.

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.

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