Abstract
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 through 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 a stronger matrix-degrading capability. Podosome rosette fission may be the result of polarized myosin II-mediated contractility of these structures, which is coordinately regulated by myosin light chain kinase and Rho-associated kinase II. Collectively, this study unveils a previously unknown mechanism—fission for the biogenesis of podosome rosettes.
Highlights
Podosomes are dynamic actin-based membrane protrusions that are important for extracellular matrix degradation and invasive cell motility
Transient expression of green fluorescent protein (GFP)-MLC kinase (MLCK) inhibited the formation of podosome rosettes, but enhanced the formation of the membrane cortical F-actin (Fig. 8B). These results suggest that enforced formation of stress fibers and cortical actin cytoskeleton by Rho-associated kinase (ROCK) and MLCK, respectively, counteracts the formation of podosome rosettes
Our results demonstrate that fission is a more efficient way than de novo assembly to generate new podosome rosettes and to facilitate cell invasion
Summary
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. We show that new podosome rosettes arise through one of two mechanisms; de novo assembly or fission of a pre-existing podosome rosette in Src-transformed fibroblasts. We surprisingly found that new podosome rosettes can be generated by fission of pre-existing podosome rosettes in Src-transformed fibroblasts. This phenomenon has never been described and represents a novel mechanism for the biogenesis of podosome rosettes
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