Journal article
The exocyst controls lysosome secretion and antigen extraction at the immune synapse of B cells
The Journal of cell biology, Vol.218(7), pp.2247-2264
07/01/2019
DOI: 10.1083/jcb.201811131
PMCID: PMC6605794
PMID: 31197029
Abstract
B lymphocytes capture antigens from the surface of presenting cells by forming an immune synapse. Local secretion of lysosomes, which are guided to the synaptic membrane by centrosome repositioning, can facilitate the extraction of immobilized antigens. However, the molecular basis underlying their delivery to precise domains of the plasma membrane remains elusive. Here we show that microtubule stabilization, triggered by engagement of the B cell receptor, acts as a cue to release centrosome-associated Exo70, which is redistributed to the immune synapse. This process is coupled to the recruitment and activation of GEF-H1, which is required for assembly of the exocyst complex, used to promote tethering and fusion of lysosomes at the immune synapse. B cells silenced for GEF-H1 or Exo70 display defective lysosome secretion, which results in impaired antigen extraction and presentation. Thus, centrosome repositioning coupled to changes in microtubule stability orchestrates the spatial-temporal distribution of the exocyst complex to promote polarized lysosome secretion at the immune synapse.
Details
- Title: Subtitle
- The exocyst controls lysosome secretion and antigen extraction at the immune synapse of B cells
- Creators
- Juan José Sáez - Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, ChileJheimmy Diaz - Department of Cellular and Molecular Biology, Faculty of Sciences, Pontificia Universidad Católica de Chile, Santiago, ChileJorge Ibañez - Department of Cellular and Molecular Biology, Faculty of Sciences, Pontificia Universidad Católica de Chile, Santiago, ChileJuan Pablo Bozo - Department of Cellular and Molecular Biology, Faculty of Sciences, Pontificia Universidad Católica de Chile, Santiago, ChileFernanda Cabrera Reyes - Department of Cellular and Molecular Biology, Faculty of Sciences, Pontificia Universidad Católica de Chile, Santiago, ChileMartina Alamo - Department of Cellular and Molecular Biology, Faculty of Sciences, Pontificia Universidad Católica de Chile, Santiago, ChileFrançois-Xavier Gobert - INSERM U932, Institut Curie, Centre de Recherche, PSL Research University, Paris, Île-de-France, FranceDorian Obino - INSERM U932, Institut Curie, Centre de Recherche, PSL Research University, Paris, Île-de-France, FranceMaría Rosa Bono - Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, ChileAna-María Lennon-Duménil - INSERM U932, Institut Curie, Centre de Recherche, PSL Research University, Paris, Île-de-France, FranceCharles Yeaman - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IAMaría-Isabel Yuseff - Department of Cellular and Molecular Biology, Faculty of Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile myuseff@bio.puc.cl
- Resource Type
- Journal article
- Publication Details
- The Journal of cell biology, Vol.218(7), pp.2247-2264
- Publisher
- United States
- DOI
- 10.1083/jcb.201811131
- PMID
- 31197029
- PMCID
- PMC6605794
- ISSN
- 0021-9525
- eISSN
- 1540-8140
- Grant note
- P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 07/01/2019
- Academic Unit
- Anatomy and Cell Biology; Internal Medicine
- Record Identifier
- 9984025478302771
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