Confinement sensing and signal optimization via Piezo1/PKA and myosin II pathways

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  • dc.contributor.author Hung, Wei-Chienca
  • dc.contributor.author Yang, Jessica R.ca
  • dc.contributor.author Yankaskas, Christopher L.ca
  • dc.contributor.author Wong, Bin Shengca
  • dc.contributor.author Wu, Pei-Hsunca
  • dc.contributor.author Pardo Pastor, Carlosca
  • dc.contributor.author Serra Pascual, Selma A., 1981-ca
  • dc.contributor.author Chiang, Meng-Jungca
  • dc.contributor.author Gu, Zhizhanca
  • dc.contributor.author Wirtz, Denisca
  • dc.contributor.author Valverde, M. A. (Miguel Ángel), 1963-ca
  • dc.contributor.author Zhang, Jinca
  • dc.contributor.author Konstantopoulos, Konstantinosca
  • dc.date.accessioned 2016-06-15T12:56:42Z
  • dc.date.available 2016-06-15T12:56:42Z
  • dc.date.issued 2016
  • dc.description.abstract Cells adopt distinct signaling pathways to optimize cell locomotion in different physical microenvironments. However, the underlying mechanism that enables cells to sense and respond to physical confinement is unknown. Using microfabricated devices and substrate-printing methods along with FRET-based biosensors, we report that, as cells transition from unconfined to confined spaces, intracellular Ca(2+) level is increased, leading to phosphodiesterase 1 (PDE1)-dependent suppression of PKA activity. This Ca(2+) elevation requires Piezo1, a stretch-activated cation channel. Moreover, differential regulation of PKA and cell stiffness in unconfined versus confined cells is abrogated by dual, but not individual, inhibition of Piezo1 and myosin II, indicating that these proteins can independently mediate confinement sensing. Signals activated by Piezo1 and myosin II in response to confinement both feed into a signaling circuit that optimizes cell motility. This study provides a mechanism by which confinement-induced signaling enables cells to sense and adapt to different physical microenvironments.ca
  • dc.description.sponsorship The research is supported by awards from the NIH (R01 DK073368 and DP1 CA174423 to J.Z. and R01 CA183804 and R01 GM114675 to K.K.); Kleberg Foundation and American Heart Association (to K.K.); Spanish Ministry of Economy and Competitiveness (SAF2012-38140 and SAF2015-69762-R); Fondo de Investigación Sanitaria (RD12/0042/0014); and FEDER Funds (to M.A.V.).
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Hung WC, Yang JR, Yankaskas CL, Wong BS, Wu PH, Pardo-Pastor C et al. Confinement sensing and signal optimization via Piezo1/PKA and myosin II pathways. Cell reports. 2016;15(7):1430-41. DOI: 10.1016/j.celrep.2016.04.035ca
  • dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2016.04.035
  • dc.identifier.issn 2211-1247
  • dc.identifier.uri http://hdl.handle.net/10230/26917
  • dc.language.iso engca
  • dc.publisher Elsevierca
  • dc.relation.ispartof Cell reports. 2016;15(7):1430-41
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2012-38140
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-69762-R
  • dc.rights © 2016 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).ca
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/ca
  • dc.subject.other Cèl·lulesca
  • dc.title Confinement sensing and signal optimization via Piezo1/PKA and myosin II pathwaysca
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca

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