4.5 Article

Switching between blebbing and lamellipodia depends on the degree of non-muscle myosin II activity

期刊

JOURNAL OF CELL SCIENCE
卷 134, 期 1, 页码 -

出版社

COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.248732

关键词

Blebbing; Lamellipodia; Membrane protrusive activity; Non-muscle myosin II; Rho kinase; Myosin regulatory light chain kinase

资金

  1. Council of Scientific and Industrial Research, India
  2. Department of Science and Technology, Ministry of Science and Technology, India [EMR/2015/002054]
  3. IACS

向作者/读者索取更多资源

Cells can transition between blebbing and lamellipodia modes of migration by regulating the activity of ROCK and MLCK, which play a key role in determining cell migration behaviors.
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.

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