RAC1-Dependent ORAI1 Translocation to the Leading Edge Supports Lamellipodia Formation and Directional Persistence
Autor: | Irene Sanchez-Lopez, Noelia Espinosa-Bermejo, Thomas Macartney, Carlos Pascual-Caro, Lola Rodríguez-Ruiz, Yolanda Orantos-Aguilera, Francisco Javier Martin-Romero, Eulalia Pozo-Guisado, Victoriano Mulero, Aida M. Lopez-Guerrero, Ana B. Pérez-Oliva |
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Rok vydání: | 2020 |
Předmět: |
rac1 GTP-Binding Protein
Leading edge ORAI1 Protein Membrane ruffling lcsh:Medicine RAC1 macromolecular substances Article Actin-Related Protein 2-3 Complex Cell Movement Epidermal growth factor Cell Line Tumor Animals Humans Neoplasm Invasiveness Pseudopodia lcsh:Science Actin Adaptor Proteins Signal Transducing Osteosarcoma Multidisciplinary biology Chemistry Calcium signalling Cell Membrane lcsh:R Cell migration Lamellipodia Cell biology Actin Cytoskeleton biology.protein lcsh:Q Lamellipodium Cortactin |
Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-18 (2020) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | Tumor invasion requires efficient cell migration, which is achieved by the generation of persistent and polarized lamellipodia. The generation of lamellipodia is supported by actin dynamics at the leading edge where a complex of proteins known as the WAVE regulatory complex (WRC) promotes the required assembly of actin filaments to push the front of the cell ahead. By using an U2OS osteosarcoma cell line with high metastatic potential, proven by a xenotransplant in zebrafish larvae, we have studied the role of the plasma membrane Ca2+ channel ORAI1 in this process. We have found that epidermal growth factor (EGF) triggered an enrichment of ORAI1 at the leading edge, where colocalized with cortactin (CTTN) and other members of the WRC, such as CYFIP1 and ARP2/3. ORAI1-CTTN co-precipitation was sensitive to the inhibition of the small GTPase RAC1, an upstream activator of the WRC. RAC1 potentiated ORAI1 translocation to the leading edge, increasing the availability of surface ORAI1 and increasing the plasma membrane ruffling. The role of ORAI1 at the leading edge was studied in genetically engineered U2OS cells lacking ORAI1 expression that helped us to prove the key role of this Ca2+ channel on lamellipodia formation, lamellipodial persistence, and cell directness, which are required for tumor cell invasiveness in vivo. |
Databáze: | OpenAIRE |
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