Mechanotransmission and Mechanosensing of Human Alpha-actinin 1
50 Pages Posted: 5 Apr 2018 Publication Status: PublishedMore...
α-actinins, a family of critical cytoskeletal actin-binding proteins that usually exist as anti-parallel dimers, play crucial roles in organizing the framework of the cytoskeleton through crosslinking the actin filaments, as well as in focal adhesion maturation. However, the molecular mechanisms underlying its functions are unclear. In this work, by mechanical manipulation of single human α-actinin 1 using magnetic tweezers, we determined the mechanical stability and kinetics of the functional domains in α-actinin 1 as well as the mechanical strength of the α-actinin 1 dimerization interaction. Moreover, we identified the force-dependence of vinculin binding to α-actinin 1, with the demonstration that force is required to expose the high-affinity binding site for vinculin binding. Based on the mechanical stability and kinetics of α-actinin 1, a novel role of the α-actinin 1 as molecular suspensions for the cytoskeleton network is revealed. Our results provide the first comprehensive analysis of the force dependent stability and interactions of α-actinin 1, which sheds new light on the molecular mechanisms underlying its mechanotransmission and mechanosensing functions.
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