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Myosin-II mediated traction forces evoke localized Piezo1-dependent Ca2+ flickers.

  • Author(s): Ellefsen, Kyle L
  • Holt, Jesse R
  • Chang, Alice C
  • Nourse, Jamison L
  • Arulmoli, Janahan
  • Mekhdjian, Armen H
  • Abuwarda, Hamid
  • Tombola, Francesco
  • Flanagan, Lisa A
  • Dunn, Alexander R
  • Parker, Ian
  • Pathak, Medha M
  • et al.
Abstract

Piezo channels transduce mechanical stimuli into electrical and chemical signals to powerfully influence development, tissue homeostasis, and regeneration. Studies on Piezo1 have largely focused on transduction of "outside-in" mechanical forces, and its response to internal, cell-generated forces remains poorly understood. Here, using measurements of endogenous Piezo1 activity and traction forces in native cellular conditions, we show that cellular traction forces generate spatially-restricted Piezo1-mediated Ca2+ flickers in the absence of externally-applied mechanical forces. Although Piezo1 channels diffuse readily in the plasma membrane and are widely distributed across the cell, their flicker activity is enriched near force-producing adhesions. The mechanical force that activates Piezo1 arises from Myosin II phosphorylation by Myosin Light Chain Kinase. We propose that Piezo1 Ca2+ flickers allow spatial segregation of mechanotransduction events, and that mobility allows Piezo1 channels to explore a large number of mechanical microdomains and thus respond to a greater diversity of mechanical cues.

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