A RhoA and Rnd3 cycle regulates actin reassembly during membrane blebbing

Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):E1863-71. doi: 10.1073/pnas.1600968113. Epub 2016 Mar 14.


The actin cytoskeleton usually lies beneath the plasma membrane. When the membrane-associated actin cytoskeleton is transiently disrupted or the intracellular pressure is increased, the plasma membrane detaches from the cortex and protrudes. Such protruded membrane regions are called blebs. However, the molecular mechanisms underlying membrane blebbing are poorly understood. This study revealed that epidermal growth factor receptor kinase substrate 8 (Eps8) and ezrin are important regulators of rapid actin reassembly for the initiation and retraction of protruded blebs. Live-cell imaging of membrane blebbing revealed that local reassembly of actin filaments occurred at Eps8- and activated ezrin-positive foci of membrane blebs. Furthermore, we found that a RhoA-ROCK-Rnd3 feedback loop determined the local reassembly sites of the actin cortex during membrane blebbing.

Keywords: Eps8; Rnd3; actin cortex; cell migration; membrane bleb.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / chemistry
  • Actin Cytoskeleton / metabolism*
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Cell Line
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism*
  • Cytoskeletal Proteins / metabolism
  • Feedback, Physiological
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Microscopy, Fluorescence
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism*
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • EPS8 protein, human
  • ezrin
  • RHOA protein, human
  • Green Fluorescent Proteins
  • ROCK1 protein, human
  • rho-Associated Kinases
  • RND3 protein, human
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein