Ankyrin-B is a PI3P effector that promotes polarized α5β1-integrin recycling via recruiting RabGAP1L to early endosomes
- Duke University Medical Center, United States
- The University of North Carolina at Chapel Hil, United States
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
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.
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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Ankyrin-B is a PI3P effector that promotes polarized α5β1-integrin recycling via recruiting RabGAP1L to early endosomes
eLife 5:e20417.
https://doi.org/10.7554/eLife.20417
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