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Regulation of actin catch-slip bonds with a RhoA-formin module
Journal article   Open access   Peer reviewed

Regulation of actin catch-slip bonds with a RhoA-formin module

Cho-Yin Lee, Jizhong Lou, Kuo-Kuang Wen, Melissa McKane, Suzanne G Eskin, Peter A Rubenstein, Shu Chien, Shoichiro Ono, Cheng Zhu and Larry V McIntire
Scientific reports, Vol.6(1), pp.35058-35058
10/12/2016
DOI: 10.1038/srep35058
PMCID: PMC5059732
PMID: 27731359
url
https://doi.org/10.1038/srep35058View
Published (Version of record) Open Access

Abstract

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-slip bonds mediated by force-induced K113:E195 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 K113:E195 interaction when formin binds to actin K118 and E117 residues located at the helical segment extending to K113. Actin catch-slip bonds are suppressed by single residue replacements K113E and E195K that interrupt the force-induced K113:E195 interaction; and this suppression is rescued by a K113E/E195K double mutant (E/K) 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 E/K. 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.
Microfilament Proteins - chemistry rhoA GTP-Binding Protein - chemistry Actins - metabolism Gene Expression Regulation Models, Molecular rhoA GTP-Binding Protein - metabolism Molecular Dynamics Simulation Lysine - genetics Animals Actins - chemistry Protein Binding Microfilament Proteins - metabolism Binding Sites Amino Acid Substitution

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