TY - JOUR TI - Ankyrin-B is a PI3P effector that promotes polarized α5β1-integrin recycling via recruiting RabGAP1L to early endosomes AU - Qu, Fangfei AU - Lorenzo, Damaris N AU - King, Samantha J AU - Brooks, Rebecca AU - Bear, James E AU - Bennett, Vann A2 - Ivaska, Johanna VL - 5 PY - 2016 DA - 2016/10/08 SP - e20417 C1 - eLife 2016;5:e20417 DO - 10.7554/eLife.20417 UR - https://doi.org/10.7554/eLife.20417 AB - 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. KW - Endosomal transport KW - α5β1-integrin KW - Ankyrin-B KW - RabGAP1L KW - haptotaxis JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -