First Author | Qu F | Year | 2016 |
Journal | Elife | Volume | 5 |
PubMed ID | 27718357 | Mgi Jnum | J:238624 |
Mgi Id | MGI:5823289 | Doi | 10.7554/eLife.20417 |
Citation | Qu F, et al. (2016) Ankyrin-B is a PI3P effector that promotes polarized alpha5beta1-integrin recycling via recruiting RabGAP1L to early endosomes. Elife 5:e20417 |
abstractText | 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 alpha5beta1-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 alpha5beta1-integrin depends on an AnkB/RabGAP1L complex for polarized recycling. Our results reveal AnkB as an unexpected key element in coordinating polarized transport of alpha5beta1-integrin and likely of other specialized endocytic cargos. |