Cells can adopt both mesenchymal and amoeboid modes of migration through membrane protrusive activities, namely formation of lamellipodia and blebbing. How the molecular players control the transition between lamellipodia and blebs is yet to be explored. Here, we show that addition of the ROCK inhibitor Y27632 or low doses of blebbistatin, an inhibitor of non-muscle myosin II (NMII) ATPase activity and filament partitioning, induces blebbing to lamellipodia conversion (BLC), whereas addition of low doses of ML7, an inhibitor of myosin light chain kinase (MLCK), induces lamellipodia to blebbing conversion (LBC) in human MDA-MB-231 cells. Similarly, siRNA-mediated knockdown of ROCK and MLCK induces BLC and LBC, respectively. Interestingly, both blebs and lamellipodia membrane protrusions are able to maintain the ratio of phosphorylated to unphosphorylated regulatory light chain at cortices when MLCK and ROCK, respectively, are inhibited either pharmacologically or genetically, suggesting that MLCK and ROCK activities are interlinked in BLC and LBC. Such BLCs and LBCs are also inducible in other cell lines, including MCF7 and MCF10A. These studies reveal that the relative activity of ROCK and MLCK, which controls both the ATPase activity and filament-forming property of NMII, is a determining factor in whether a cell exhibits blebbing or lamellipodia.

细胞可以通过膜突出活动，即形成片状脂质体和起泡，采用间充质和变形虫的迁移方式。分子参与者如何控制lamellipodia和气泡之间的过渡尚待探索。在这里，我们显示了添加ROCK抑制剂Y27632或低剂量的非肌肉肌球蛋白II（NMII）ATPase活性和细丝分配抑制剂blebbistatin会导致泡沫向片状脂蛋白转化（BLC），而添加低剂量的ML7 ，肌球蛋白轻链激酶（MLCK）的抑制剂，可诱导人MDA-MB-231细胞中的片状脂蛋白向起泡转化（LBC）。同样，siRNA介导的ROCK和MLCK的敲低分别诱导BLC和LBC。有趣的是 当MLCK和ROCK分别在药理或遗传上受到抑制时，气泡和片状脂膜的突起均能够维持皮质中磷酸化与未磷酸化的调节轻链的比率，这表明MLCK和ROCK活性在BLC和LBC中相互关联。此类BLC和LBC在其他细胞系（包括MCF7和MCF10A）中也可诱导。这些研究表明，ROCK和MLCK的相对活性控制着NMII的ATPase活性和细丝形成特性，是决定细胞是否显示起泡或片状脂溢的决定因素。此类BLC和LBC在其他细胞系（包括MCF7和MCF10A）中也可诱导。这些研究表明，ROCK和MLCK的相对活性控制着NMII的ATPase活性和细丝形成特性，是决定细胞是否显示起泡或片状脂溢的决定因素。此类BLC和LBC在其他细胞系（包括MCF7和MCF10A）中也可诱导。这些研究表明，ROCK和MLCK的相对活性控制着NMII的ATPase活性和细丝形成特性，是决定细胞是否显示起泡或片状脂溢的决定因素。