Regulation of Actin Catch-Slip Bonds with a RhoA-formin Module
Journal Article - Open Access
Emory University Atlanta United States
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The dynamic turnover of the actin cytoskeleton is regulated cooperatively by force and biochemical signaling. We previously demonstrated that actin depolymerization under force is governed by catch slipbonds mediated by force-induced K113E195 salt-bridges. Yet, the biochemical regulation as well as the functional significance of actin catch bonds has not been elucidated. Using AFM force-clamp experiments, we show that formin controlled by RhoA switches the actin catch-slip bonds to slip-only bonds. SMD simulations reveal that the force does not induce the K113E195 interaction when formin binds to actin K118 and E117 residues located at the helical segment extending to K113. Actin catch slipbonds are suppressed by single residue replacements K113E and E195K that interrupt the force induced K113E195 interaction and this suppression is rescued by a K113EE195K double mutant EK restoring the interaction in the opposite orientation. These results support the biological significance of actin catch bonds, as they corroborate reported observations that RhoA and formin switch force induced actin cytoskeleton alignment and that either K113E or E195K induces yeast cell growth defects rescued by EK. Our study demonstrates how the mechano-regulation of actin dynamics is modulated by biochemical signaling molecules, and suggests that actin catch bonds may be important in cell functions.