Mechanotransmission and Mechanosensing of Human alpha-Actinin 1

Shimin Le, Xian Hu, Mingxi Yao, Hu Chen, Miao Yu, Xiaochun Xu, Naotaka Nakazawa, Felix M. Margadant, Michael Sheetz, Jie Yan

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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. Here, 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. 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. Further, a role of the α-actinin 1 as molecular shock absorber for the cytoskeleton network is revealed. Our results provide a comprehensive analysis of the force-dependent stability and interactions of α-actinin 1, which sheds important light on the molecular mechanisms underlying its mechanotransmission and mechanosensing functions. α-Actinins are critical actin crosslinking proteins that organize actin cytoskeletal networks. Le et al. determine the mechanical stability and dynamics of human α-actinin 1 and the force-dependence of vinculin binding to α-actinin 1, which sheds light on the molecular mechanisms of mechanotransmission and mechanosensing.

Original languageEnglish (US)
Pages (from-to)2714-2723
Number of pages10
JournalCell Reports
Volume21
Issue number10
DOIs
StatePublished - Dec 5 2017
Externally publishedYes

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Keywords

  • cytoskeleton
  • magnetic tweezers
  • mechanosensing
  • mechanostransmission
  • molecular shock absorber
  • single molecule manipulation
  • vinculin binding
  • α-actinin 1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Le, S., Hu, X., Yao, M., Chen, H., Yu, M., Xu, X., Nakazawa, N., Margadant, F. M., Sheetz, M., & Yan, J. (2017). Mechanotransmission and Mechanosensing of Human alpha-Actinin 1. Cell Reports, 21(10), 2714-2723. https://doi.org/10.1016/j.celrep.2017.11.040