Actin depolymerization under force is governed by lysine 113:glutamic acid 195-mediated catch-slip bonds

Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):5022-7. doi: 10.1073/pnas.1218407110. Epub 2013 Mar 4.

Abstract

As a key element in the cytoskeleton, actin filaments are highly dynamic structures that constantly sustain forces. However, the fundamental question of how force regulates actin dynamics is unclear. Using atomic force microscopy force-clamp experiments, we show that tensile force regulates G-actin/G-actin and G-actin/F-actin dissociation kinetics by prolonging bond lifetimes (catch bonds) at a low force range and by shortening bond lifetimes (slip bonds) beyond a threshold. Steered molecular dynamics simulations reveal force-induced formation of new interactions that include a lysine 113(K113):glutamic acid 195 (E195) salt bridge between actin subunits, thus suggesting a molecular basis for actin catch-slip bonds. This structural mechanism is supported by the suppression of the catch bonds by the single-residue replacements K113 to serine (K113S) and E195 to serine (E195S) on yeast actin. These results demonstrate and provide a structural explanation for actin catch-slip bonds, which may provide a mechanoregulatory mechanism to control cell functions by regulating the depolymerization kinetics of force-bearing actin filaments throughout the cytoskeleton.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actin Cytoskeleton / chemistry*
  • Actin Cytoskeleton / genetics
  • Actin Cytoskeleton / ultrastructure
  • Actins / chemistry*
  • Actins / genetics
  • Amino Acid Substitution
  • Animals
  • Avian Proteins / chemistry
  • Avian Proteins / genetics
  • Chickens
  • Humans
  • Microscopy, Atomic Force
  • Mutation, Missense
  • Rabbits
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics

Substances

  • Actins
  • Avian Proteins
  • Saccharomyces cerevisiae Proteins