| Summary: | 碩士 === 國立中興大學 === 生命科學系所 === 105 === Podosomes are dynamic actin-based membrane protrusions that are important for extracellular matrix degradation and invasive cell motility. Individual podosomes are often found to organize into large rosette-like structures in some types of cells, such as osteoclasts, endothelial cells, Src-transformed fibroblasts, and certain highly invasive cancer cells. In this study, we show that new podosome rosettes arise by one of two mechanisms; de novo assembly or fission of a pre-existing podosome rosette in Src-transformed fibroblasts. Fission is a more efficient way than de novo assembly to generate new podosome rosettes in these cells. Podosome rosettes undergoing fission possess higher motility and stronger matrix-degrading capability. Podosome rosette fission may be the result of polarized myosin II-mediated contractility of these structures. Moreover, we found that the fission of podosome rosettes is inhibited by suppression of myosin light chain kinase (MLCK), but increased by suppression of Rho-associated kinase II (ROCK II). Take together, this study unveils a previously unknown mechanism—fission for the biogenesis of podosome rosettes and suggests a positive role for MLCK and a negative role for ROCK II in this process.
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