Hic-5 regulates Src-induced invadopodia rosette formation and organization
| Autor: | Christopher E. Turner, Ian J. Forsythe, Anushree C. Gulvady |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Scaffold protein
Fetal Proteins rac1 GTP-Binding Protein Rosette Formation Formins RAC1 Biology 03 medical and health sciences Mice Live cell imaging Animals Kinase activity Phosphorylation Molecular Biology Paxillin 030304 developmental biology Cell Line Transformed Myosin Type II 0303 health sciences 030302 biochemistry & molecular biology Neuropeptides Cell Biology Articles Fibroblasts LIM Domain Proteins Actins Cell biology DNA-Binding Proteins Cell Motility Cytoskeletal Proteins src-Family Kinases Focal Adhesion Protein-Tyrosine Kinases Invadopodia Podosomes biology.protein NIH 3T3 Cells Protein Processing Post-Translational Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | Fibroblasts transformed by the proto-oncogene Src form individual invadopodia that can spontaneously self-organize into large matrix-degrading superstructures called rosettes. However, the mechanisms by which the invadopodia can spatiotemporally reorganize their architecture is not well understood. Here, we show that Hic-5, a close relative of the scaffold protein paxillin, is essential for the formation and organization of rosettes in active Src-transfected NIH3T3 fibroblasts and cancer-associated fibroblasts. Live cell imaging, combined with domain-mapping analysis of Hic-5, identified critical motifs as well as phosphorylation sites that are required for the formation and dynamics of rosettes. Using pharmacological inhibition and mutant expression, we show that FAK kinase activity, along with its proximity to and potential interaction with the LD2,3 motifs of Hic-5, is necessary for rosette formation. Invadopodia dynamics and their coalescence into rosettes were also dependent on Rac1, formin, and myosin II activity. Superresolution microscopy revealed the presence of formin FHOD1 and INF2-mediated unbranched radial F-actin fibers emanating from invadopodia and rosettes, which may facilitate rosette formation. Collectively, our data highlight a novel role for Hic-5 in orchestrating the organization of invadopodia into higher-order rosettes, which may promote the localized matrix degradation necessary for tumor cell invasion. |
| Databáze: | OpenAIRE |
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