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Confinement Sensing and Signal Optimization via Piezo1/PKA and Myosin II Pathways.
Hung, Wei-Chien; Yang, Jessica R; Yankaskas, Christopher L; Wong, Bin Sheng; Wu, Pei-Hsun; Pardo-Pastor, Carlos; Serra, Selma A; Chiang, Meng-Jung; Gu, Zhizhan; Wirtz, Denis; Valverde, Miguel A; Yang, Joy T; Zhang, Jin; Konstantopoulos, Konstantinos.
Afiliação
  • Hung WC; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Yang JR; Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Yankaskas CL; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Wong BS; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Wu PH; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Pardo-Pastor C; Laboratory of Molecular Physiology and Channelopathies, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Carrera del Doctor Aiguader 88, Barcelona 08003, Spain.
  • Serra SA; Laboratory of Molecular Physiology and Channelopathies, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Carrera del Doctor Aiguader 88, Barcelona 08003, Spain.
  • Chiang MJ; Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Gu Z; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Wirtz D; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Valverde MA; Laboratory of Molecular Physiology and Channelopathies, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Carrera del Doctor Aiguader 88, Barcelona 08003, Spain.
  • Yang JT; Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: jyang@jhmi.edu.
  • Zhang J; Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: jzhang32@ucsd.edu.
  • Konstantopoulos K; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic
Cell Rep ; 15(7): 1430-1441, 2016 05 17.
Article em En | MEDLINE | ID: mdl-27160899
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Movimento Celular / Proteínas Quinases Dependentes de AMP Cíclico / Miosina Tipo II / Canais Iônicos Limite: Animals Idioma: En Revista: Cell Rep Ano de publicação: 2016 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Movimento Celular / Proteínas Quinases Dependentes de AMP Cíclico / Miosina Tipo II / Canais Iônicos Limite: Animals Idioma: En Revista: Cell Rep Ano de publicação: 2016 Tipo de documento: Article