An IFT20 mechanotrafficking axis is required for integrin recycling, focal adhesion dynamics, and polarized cell migration
| Autor: | Ellen J. Ezratty, Salma Begum, Steven Su |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Keratinocytes
Male Integrins Endosome Integrin Mice Inbred Strains Endosomes Biology Mechanotransduction Cellular Microtubules Focal adhesion Mice 03 medical and health sciences 0302 clinical medicine Cell Movement Intraflagellar transport Cell Adhesion Animals Cilia Keratinocyte migration Mechanotransduction Molecular Biology 030304 developmental biology Focal Adhesions Wound Healing 0303 health sciences Integrin beta1 Cell Membrane Cell Polarity Cell migration Articles Cell Biology Cell biology Protein Transport Cell Motility 030220 oncology & carcinogenesis biology.protein Female Carrier Proteins Wound healing |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e20-04-0232 |
| Popis: | Directional cell migration drives embryonic development, cancer metastasis, and tissue repair and regeneration. Here, we examine the role of intraflagellar transport (IFT) 20 (Ift20) during polarized migration of epidermal cells. IFT20 is implicated in regulating cell migration independently of the primary cilium, but how IFT proteins integrate with the cell migration machinery is poorly understood. We show that genetic ablation of IFT20 in vitro slows keratinocyte migration during wound healing. We find that this phenotype is independent of the primary cilium and instead can be attributed to alterations in integrin-mediated mechanotransduction and focal adhesion (FA) dynamics. Loss of Ift20 resulted in smaller and less numerous FAs and reduced the levels of activated FA kinase. Studies of FA dynamics during microtubule-induced FA turnover demonstrated that Ift20 loss specifically impaired the reformation, but not the disassembly, of FAs. In the absence of Ift20 function, β1 integrins endocytosed during FA disassembly are not transferred out of Rab5 (+) endosomes. This defective transit from the early endosome disrupts eventual recycling of β1 integrins back to the cell surface, resulting in defective FA reformation. In vivo, conditional ablation of Ift20 in hair follicle stem cells (HF-SCs) similarly impairs their ability to invade and migrate during epidermal wound healing. Using explant studies, lineage tracing, and clonal analysis, we demonstrate that Ift20 is required for HF-SC migration and their contribution to epidermal regeneration. This work identifies a new Ift20 mechanotrafficking mechanism required for polarized cell migration and stem cell–driven tissue repair. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|