1. Immunology and Inflammation
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Protein sorting by lipid phase-like domains supports emergent signaling function in B lymphocyte plasma membranes

  1. Matthew B Stone
  2. Sarah A Shelby
  3. Marcos F Núñez
  4. Kathleen Wisser
  5. Sarah L Veatch  Is a corresponding author
  1. University of Michigan, United States
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Cite this article as: eLife 2017;6:e19891 doi: 10.7554/eLife.19891

Abstract

Diverse cellular signaling events, including B cell receptor (BCR) activation, are hypothesized to be facilitated by domains enriched in specific plasma membrane lipids and proteins that resemble liquid-ordered phase-separated domains in model membranes. This concept remains controversial and lacks direct experimental support in intact cells. Here, we visualize ordered and disordered domains in mouse B lymphoma cell membranes using super-resolution fluorescence localization microscopy, demonstrate that clustered BCR resides within ordered phase-like domains capable of sorting key regulators of BCR activation, and present a minimal, predictive model where clustering receptors leads to their collective activation by stabilizing an extended ordered domain. These results provide evidence for the role of membrane domains in BCR signaling and a plausible mechanism of BCR activation via receptor clustering that could be generalized to other signaling pathways. Overall, these studies demonstrate that lipid mediated forces can bias biochemical networks in ways that broadly impact signal transduction.

Article and author information

Author details

  1. Matthew B Stone

    Department of Biophysics, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Sarah A Shelby

    Department of Biophysics, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Marcos F Núñez

    Department of Biophysics, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Kathleen Wisser

    Department of Biophysics, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Sarah L Veatch

    Department of Biophysics, University of Michigan, Ann Arbor, United States
    For correspondence
    sveatch@umich.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9317-2308

Funding

National Institute of General Medical Sciences (R01GM110052)

  • Sarah L Veatch

National Science Foundation (MCB 1552439)

  • Sarah L Veatch

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments were performed in compliance with federal laws and institutional guidelines as approved by the University Committee on Use and Care of Animals (protocol #PRO00005048).

Reviewing Editor

  1. Michael L Dustin, University of Oxford, United Kingdom

Publication history

  1. Received: July 22, 2016
  2. Accepted: January 31, 2017
  3. Accepted Manuscript published: February 1, 2017 (version 1)
  4. Version of Record published: March 30, 2017 (version 2)

Copyright

© 2017, Stone et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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