1. Biochemistry and Chemical Biology
  2. Cell Biology
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Ankyrin-B is a PI3P effector that promotes polarized α5β1-integrin recycling via recruiting RabGAP1L to early endosomes

  1. Fangfei Qu
  2. Damaris N Lorenzo
  3. Samantha J King
  4. Rebecca Brooks
  5. James E Bear
  6. Vann Bennett  Is a corresponding author
  1. Duke University Medical Center, United States
  2. The University of North Carolina at Chapel Hil, United States
Research Article
  • Cited 10
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Cite this article as: eLife 2016;5:e20417 doi: 10.7554/eLife.20417

Abstract

Endosomal membrane trafficking requires coordination between phosphoinositide lipids, Rab GTPases, and microtubule-based motors to dynamically determine endosome identity and promote long-range organelle transport. Here we report that Ankyrin-B (AnkB), through integrating all three systems, functions as a critical node in the protein circuitry underlying polarized recycling of α5β1-integrin in mouse embryonic fibroblasts, which enables persistent fibroblast migration along fibronectin gradients. AnkB associates with phosphatidylinositol 3-phosphate (PI3P)-positive organelles in fibroblasts and binds dynactin to promote their long-range motility. We demonstrate that AnkB binds to Rab GTPase Activating Protein 1-Like (RabGAP1L) and recruits it to PI3P-positive organelles, where RabGAP1L inactivates Rab22A, and promotes polarized trafficking to the leading edge of migrating fibroblasts. We further determine that α5β1-integrin depends on an AnkB/RabGAP1L complex for polarized recycling. Our results reveal AnkB as an unexpected key element in coordinating polarized transport of α5β1-integrin and likely of other specialized endocytic cargos.

Article and author information

Author details

  1. Fangfei Qu

    Department of Cell Biology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Damaris N Lorenzo

    Department of Cell Biology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Samantha J King

    UNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hil, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Rebecca Brooks

    UNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hil, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. James E Bear

    UNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hil, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Vann Bennett

    Department of Cell Biology, Duke University Medical Center, Durham, United States
    For correspondence
    vann.bennett@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2695-7209

Funding

Howard Hughes Medical Institute

  • Fangfei Qu
  • Damaris N Lorenzo
  • Vann Bennett

National Institutes of Health (National Institute of Health grant GM110155)

  • Samantha J King
  • Rebecca Brooks
  • James E Bear

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

Ethics

Animal experimentation: This study was performed strictly following the guide for the laboratory animal care and use at Duke University Medical Center. All of the animals were handled according to approved Institutional Animal Care and Use Committee (IACUC) protocol (# A149-15-05) of Duke University.

Reviewing Editor

  1. Johanna Ivaska, University of Turku, Finland

Publication history

  1. Received: August 6, 2016
  2. Accepted: October 7, 2016
  3. Accepted Manuscript published: October 8, 2016 (version 1)
  4. Version of Record published: November 1, 2016 (version 2)

Copyright

© 2016, Qu 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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