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Ig? ubiquitination activates PI3K signals required for endosomal sorting.


ABSTRACT: A wealth of in vitro data has demonstrated a central role for receptor ubiquitination in endocytic sorting. However, how receptor ubiquitination functions in vivo is poorly understood. Herein, we report that ablation of B cell antigen receptor ubiquitination in vivo uncouples the receptor from CD19 phosphorylation and phosphatidylinositol 3-kinase (PI3K) signals. These signals are necessary and sufficient for accumulating phosphatidylinositol (3,4,5)-trisphosphate (PIP3) on B cell receptor-containing early endosomes and proper sorting into the MHC class II antigen-presenting compartment (MIIC). Surprisingly, MIIC targeting is dispensable for T cell-dependent immunity. Rather, it is critical for activating endosomal toll-like receptors and antiviral humoral immunity. These findings demonstrate a novel mechanism of receptor endosomal signaling required for specific peripheral immune responses.

SUBMITTER: Veselits M 

PROVIDER: S-EPMC5716028 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Igβ ubiquitination activates PI3K signals required for endosomal sorting.

Veselits Margaret M   Tanaka Azusa A   Chen Yaoqing Y   Hamel Keith K   Mandal Malay M   Kandasamy Matheswaran M   Manicassamy Balaji B   O'Neill Shannon K SK   Wilson Patrick P   Sciammas Roger R   Clark Marcus R MR  

The Journal of experimental medicine 20171115 12


A wealth of in vitro data has demonstrated a central role for receptor ubiquitination in endocytic sorting. However, how receptor ubiquitination functions in vivo is poorly understood. Herein, we report that ablation of B cell antigen receptor ubiquitination in vivo uncouples the receptor from CD19 phosphorylation and phosphatidylinositol 3-kinase (PI3K) signals. These signals are necessary and sufficient for accumulating phosphatidylinositol (3,4,5)-trisphosphate (PIP<sub>3</sub>) on B cell rec  ...[more]

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