Membrane ruffles in cell migration: indicators of inefficient lamellipodia adhesion and compartments of actin filament reorganization.
During epithelial cell migration, membrane ruffles can be visualized by phase contrast microscopy as dark waves arising at the leading edge of lamellipodia that move centripetally toward the main cell body. Despite the common use of the term membrane ruffles, their structure, molecular composition, and the mechanisms leading to their formation remained largely unknown. We show here that membrane ruffles differ from the underlying cell lamella by more densely packed bundles of actin filaments that are enriched in the actin cross-linkers filamin and ezrin, pointing to a specific bundling process based on these cross-linkers. The accumulation of phosphorylated, that is, inactivated, cofilin in membrane ruffles suggests that they are compartments of inhibited actin filament turnover. High Rac1 and low RhoA activities were found under conditions of suboptimal integrin-ligand interaction correlating with low lamellipodia persistence, inefficient migration, and high ruffling rates. Based on these findings, we define membrane ruffles as distinct compartments of specific composition that form as a consequence of inefficient lamellipodia adhesion.
Borm
Bodo
B
Institute for Cell Biology, University of Bonn, 53121 Bonn, Germany.
Requardt
Robert P
RP
Herzog
Volker
V
Kirfel
Gregor
G
D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D051339:Actin Depolymerizing Factors; D021961:Cell Membrane Structures / Q000378:metabolism* / Q000648:ultrastructure; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003285:Contractile Proteins / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D005353:Fibronectins / Q000378:metabolism; D064448:Filamins; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000648:ultrastructure; D008024:Ligands; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D010750:Phosphoproteins / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism* / Q000648:ultrastructure; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000099149:Ezrin
D051339:Actin Depolymerizing Factors; D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; D005353:Fibronectins; D064448:Filamins; D039081:Integrin alpha5beta1; D008024:Ligands; D008840:Microfilament Proteins; D010750:Phosphoproteins; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; D000099149:Ezrin