Ankyrin-B is a PI3P effector that promotes polarized α5β1-integrin recycling via recruiting RabGAP1L to early endosomes
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, function...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/20417 |
| _version_ | 1811200662071934976 |
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| author | Fangfei Qu Damaris N Lorenzo Samantha J King Rebecca Brooks James E Bear Vann Bennett |
| author_facet | Fangfei Qu Damaris N Lorenzo Samantha J King Rebecca Brooks James E Bear Vann Bennett |
| author_sort | Fangfei Qu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:08:32Z |
| format | Article |
| id | doaj.art-f6b562fe4bf6463b9e3fcfd3078daeac |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:08:32Z |
| publishDate | 2016-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f6b562fe4bf6463b9e3fcfd3078daeac2022-12-22T03:52:29ZengeLife Sciences Publications LtdeLife2050-084X2016-10-01510.7554/eLife.20417Ankyrin-B is a PI3P effector that promotes polarized α5β1-integrin recycling via recruiting RabGAP1L to early endosomesFangfei Qu0Damaris N Lorenzo1Samantha J King2Rebecca Brooks3James E Bear4Vann Bennett5https://orcid.org/0000-0003-2695-7209Department of Biochemistry, Duke University Medical Center, Durham, United States; Department of Cell Biology, Duke University Medical Center, Durham, United States; Department of Neurobiology, Duke University Medical Center, Durham, United States; Howard Hughes Medical Institute, Duke University Medical Center, Durham, United StatesDepartment of Biochemistry, Duke University Medical Center, Durham, United States; Department of Cell Biology, Duke University Medical Center, Durham, United States; Department of Neurobiology, Duke University Medical Center, Durham, United States; Howard Hughes Medical Institute, Duke University Medical Center, Durham, United StatesUNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Durham, United States; Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, United StatesUNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Durham, United States; Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, United StatesUNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Durham, United States; Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, United StatesDepartment of Biochemistry, Duke University Medical Center, Durham, United States; Department of Cell Biology, Duke University Medical Center, Durham, United States; Department of Neurobiology, Duke University Medical Center, Durham, United States; Howard Hughes Medical Institute, Duke University Medical Center, Durham, United StatesEndosomal 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.https://elifesciences.org/articles/20417Endosomal transportα5β1-integrinAnkyrin-BRabGAP1Lhaptotaxis |
| spellingShingle | Fangfei Qu Damaris N Lorenzo Samantha J King Rebecca Brooks James E Bear Vann Bennett Ankyrin-B is a PI3P effector that promotes polarized α5β1-integrin recycling via recruiting RabGAP1L to early endosomes eLife Endosomal transport α5β1-integrin Ankyrin-B RabGAP1L haptotaxis |
| title | Ankyrin-B is a PI3P effector that promotes polarized α5β1-integrin recycling via recruiting RabGAP1L to early endosomes |
| title_full | Ankyrin-B is a PI3P effector that promotes polarized α5β1-integrin recycling via recruiting RabGAP1L to early endosomes |
| title_fullStr | Ankyrin-B is a PI3P effector that promotes polarized α5β1-integrin recycling via recruiting RabGAP1L to early endosomes |
| title_full_unstemmed | Ankyrin-B is a PI3P effector that promotes polarized α5β1-integrin recycling via recruiting RabGAP1L to early endosomes |
| title_short | Ankyrin-B is a PI3P effector that promotes polarized α5β1-integrin recycling via recruiting RabGAP1L to early endosomes |
| title_sort | ankyrin b is a pi3p effector that promotes polarized α5β1 integrin recycling via recruiting rabgap1l to early endosomes |
| topic | Endosomal transport α5β1-integrin Ankyrin-B RabGAP1L haptotaxis |
| url | https://elifesciences.org/articles/20417 |
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