@article{d9ce15535ad0489dbdef37513454f56a,
title = "Actin-Membrane Release Initiates Cell Protrusions",
abstract = "Despite the well-established role of actin polymerization as a driving mechanism for cell protrusion, upregulated actin polymerization alone does not initiate protrusions. Using a combination of theoretical modeling and quantitative live-cell imaging experiments, we show that local depletion of actin-membrane links is needed for protrusion initiation. Specifically, we show that the actin-membrane linker ezrin is depleted prior to protrusion onset and that perturbation of ezrin's affinity for actin modulates protrusion frequency and efficiency. We also show how actin-membrane release works in concert with actin polymerization, leading to a comprehensive model for actin-driven shape changes. Actin-membrane release plays a similar role in protrusions driven by intracellular pressure. Thus, our findings suggest that protrusion initiation might be governed by a universal regulatory mechanism, whereas the mechanism of force generation determines the shape and expansion properties of the protrusion.",
keywords = "Brownian ratchet model, actin dynamics, cytoskeleton, intracellular force, lamellipodium, morphology, polymerization, protrusion, shape change, Cell Surface Extensions/metabolism, Actins/metabolism, Humans, Cells, Cultured, Stress, Mechanical, Male, Cytoskeletal Proteins/metabolism, Animals, Cell Membrane/metabolism, Cell Line, Tumor, Cytoskeleton/metabolism, Female, Mice",
author = "Welf, {Erik S.} and Miles, {Christopher E.} and Jaewon Huh and Etai Sapoznik and Joseph Chi and Driscoll, {Meghan K.} and Tadamoto Isogai and Jungsik Noh and Weems, {Andrew D.} and Theresa Pohlkamp and Kevin Dean and Reto Fiolka and Alex Mogilner and Gaudenz Danuser",
note = "Funding Information: This work was funded by the National Institute of Health ( K25CA204526 to E.S.W., F32GM116370 and K99GM123221 to M.K.D., 1F32GM117793 to K.M.D., R33CA235254 and R35 GM133522 to R.F., and R01GM071868 and R35GM136428 to G.D.), the Cancer Prevention and Research Institute of Texas ( RR160057 to R.F.), and the US Army Research Office ( W911NF-17-1-0417 to A.M.); A.D.W. is a fellow of the Jane Coffin Child{\textquoteright}s Memorial Fund. Funding Information: We would like to thank James Bear (University of North Carolina, Chapel Hill) for suggesting the PA-Rac1 experiment, Maja K?hn (Albert Ludwigs University of Freiburg, Germany) for sharing the PRL3 construct, Yi Wu (University of Connecticut Health Center, Farmington, CT) for sharing the PA-Rac1 construct and for helpful advice, and Peter Friedl (MD Anderson Cancer Center, Houston, TX) and R. McIntosh (University of Colorado Boulder CO) for sharing cell lines. We would also like to thank Mike Rosen and Sandy Schmid (UT Southwestern Medical Center Dallas TX) for helpful discussion of the manuscript. This work was funded by the National Institute of Health (K25CA204526 to E.S.W. F32GM116370 and K99GM123221 to M.K.D. 1F32GM117793 to K.M.D. R33CA235254 and R35 GM133522 to R.F. and R01GM071868 and R35GM136428 to G.D.), the Cancer Prevention and Research Institute of Texas (RR160057 to R.F.), and the US Army Research Office (W911NF-17-1-0417 to A.M.); A.D.W. is a fellow of the Jane Coffin Child's Memorial Fund. Conceptualization, E.S.W. C.J.M. A.M. and G.D.; Formal analysis, E.S.W. J.H. M.K.D. and J.N.; Investigation, C.J.M. J.H. T.I. E.S. J.C. M.K.D. J.N. and A.D.W.; Methodology, E.S.W. C.J.M. J.H. M.K.D. J.N. R.F. A.M. and G.D.; Project administration, E.S.W. Visualization, E.S.W. M.K.D. and A.D.W.; Original Draft Writing, E.S.W. C.J.M. A.M. and G.D.; Software, J.H. J.N.; Resources, J.C. T.P. K.D. R.F. and G.D.; Supervision, R.F.; Funding Acquisition, G.D. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = dec,
day = "21",
doi = "10.1016/j.devcel.2020.11.024",
language = "English (US)",
volume = "55",
pages = "723--736.e8",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "6",
}