Identification of MYO18A as a Novel Interacting Partner of the PAK2/βPIX/GIT1 Complex and Its Potential Function in Modulating Epithelial Cell Migration
| Autor: | Ping-Chiang Lyu, Ya-Ju Hsieh, Rae-Mann Hsu, Jau-Song Yu, Ming-Hung Tsai |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Stress fiber
Cell Cycle Proteins Biology Myosins Epithelial cell migration Cell Line Focal adhesion Cell Movement Stress Fibers Myosin Guanine Nucleotide Exchange Factors Humans Molecular Biology Actin Adaptor Proteins Signal Transducing Focal Adhesions Epithelial Cells Cell Biology Articles Actins Cell biology Protein Structure Tertiary Protein Transport Epidermoid carcinoma p21-Activated Kinases Multiprotein Complexes Cell Surface Extensions Lamellipodium A431 cells Rho Guanine Nucleotide Exchange Factors Protein Binding |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | MYO18A is found as a novel PAK2 binding partner via βPIX/GIT1. MYO18A-depleted cells showed dramatic changes in shape, actin stress fiber and membrane ruffle formation, and displayed increases in the number and size of focal adhesions and a decrease in cell migration, suggesting an important role of MYO18A in regulating epithelial cell migration. The p21-activated kinase (PAK) 2 is known to be involved in numerous biological functions, including the regulation of actin reorganization and cell motility. To better understand the mechanisms underlying this regulation, we herein used a proteomic approach to identify PAK2-interacting proteins in human epidermoid carcinoma A431 cells. We found that MYO18A, an emerging member of the myosin superfamily, is a novel PAK2 binding partner. Using a siRNA knockdown strategy and in vitro binding assay, we discovered that MYO18A binds to PAK2 through the βPIX/GIT1 complex. Under normal conditions, MYO18A and PAK2 colocalized in lamellipodia and membrane ruffles. Interestingly, knockdown of MYO18A in cells did not prevent formation of the PAK2/βPIX/GIT1 complex, but rather apparently changed its localization to focal adhesions. Moreover, MYO18A-depleted cells showed dramatic changes in morphology and actin stress fiber and membrane ruffle formation and displayed increases in the number and size of focal adhesions. Migration assays revealed that MYO18A-depleted cells had decreased cell motility, and reexpression of MYO18A restored their migration ability. Collectively, our findings indicate that MYO18A is a novel binding partner of the PAK2/βPIX/GIT1 complex and suggest that MYO18A may play an important role in regulating epithelial cell migration via affecting multiple cell machineries. |
| Databáze: | OpenAIRE |
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