Nanoscale integrin cluster dynamics controls cellular mechanosensing via FAKY397 phosphorylation.

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  • Additional Information
    • Source:
      Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: eCollection Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]-
    • Subject Terms:
      Mechanotransduction, Cellular*; Cellular Microenvironment/*genetics ; Epithelial Cells/*metabolism ; Extracellular Matrix/*metabolism ; Focal Adhesion Kinase 1/*metabolism ; Integrins/*metabolism; Animals ; Cell Adhesion ; Cell Differentiation ; Cell Line, Tumor ; Cell Movement ; Dogs ; Epithelial Cells/ultrastructure ; Extracellular Matrix/ultrastructure ; Focal Adhesion Kinase 1/genetics ; Gene Expression ; Humans ; Integrins/genetics ; Madin Darby Canine Kidney Cells ; Mice ; NIH 3T3 Cells ; Phosphorylation ; Species Specificity
    • Abstract:
      Transduction of extracellular matrix mechanics affects cell migration, proliferation, and differentiation. While this mechanotransduction is known to depend on the regulation of focal adhesion kinase phosphorylation on Y397 (FAKpY397), the mechanism remains elusive. To address this, we developed a mathematical model to test the hypothesis that FAKpY397-based mechanosensing arises from the dynamics of nanoscale integrin clustering, stiffness-dependent disassembly of integrin clusters, and FAKY397 phosphorylation within integrin clusters. Modeling results predicted that integrin clustering dynamics governs how cells convert substrate stiffness to FAKpY397, and hence governs how different cell types transduce mechanical signals. Existing experiments on MDCK cells and HT1080 cells, as well as our new experiments on 3T3 fibroblasts, confirmed our predictions and supported our model. Our results suggest a new pathway by which integrin clusters enable cells to calibrate responses to their mechanical microenvironment.
      (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
    • References:
      Am J Physiol Cell Physiol. 2008 Dec;295(6):C1579-89. (PMID: 18923058)
      Nat Cell Biol. 2007 Aug;9(8):905-14. (PMID: 17618274)
      J Biol Chem. 2014 Jun 27;289(26):18507-13. (PMID: 24838247)
      J Cell Biol. 2005 Oct 24;171(2):383-92. (PMID: 16247034)
      Nat Cell Biol. 2016 Sep;18(9):941-53. (PMID: 27548916)
      Nat Mater. 2019 Jun;18(6):638-649. (PMID: 31114072)
      Nat Commun. 2016 May 18;7:11642. (PMID: 27189435)
      J Cell Sci. 2017 May 1;130(9):1612-1624. (PMID: 28302906)
      Science. 2009 Jan 30;323(5914):642-4. (PMID: 19179533)
      J Cell Biol. 2009 Jun 29;185(7):1275-84. (PMID: 19564406)
      J Cell Sci. 2005 Oct 1;118(Pt 19):4415-25. (PMID: 16159962)
      Nat Mater. 2017 Jul;16(7):775-781. (PMID: 28459445)
      J Cell Biol. 2001 Dec 24;155(7):1319-32. (PMID: 11756480)
      Science. 2017 Aug 18;357(6352):703-706. (PMID: 28818948)
      Nat Mater. 2014 Jun;13(6):631-7. (PMID: 24793358)
      Nat Cell Biol. 2016 Jan;18(1):33-42. (PMID: 26619148)
      Dev Cell. 2015 Dec 7;35(5):614-621. (PMID: 26625956)
      Nat Cell Biol. 2018 Nov;20(11):1290-1302. (PMID: 30361699)
      J Cell Sci. 2007 Jan 1;120(Pt 1):137-48. (PMID: 17164291)
      Front Med (Lausanne). 2015 Sep 03;2:59. (PMID: 26389119)
      Biophys J. 2016 Nov 1;111(9):2051-2061. (PMID: 27806285)
      Cell. 1997 Jan 10;88(1):39-48. (PMID: 9019403)
      Chem Rev. 2017 Oct 25;117(20):12764-12850. (PMID: 28991456)
      Phys Rev Lett. 2000 Mar 20;84(12):2750-3. (PMID: 11017316)
      Nat Cell Biol. 2000 Apr;2(4):191-6. (PMID: 10783236)
      Nat Cell Biol. 2019 Feb;21(2):122-132. (PMID: 30602723)
      Proc Natl Acad Sci U S A. 2012 May 1;109(18):6933-8. (PMID: 22509005)
      Biophys J. 2012 Mar 7;102(5):1069-78. (PMID: 22404929)
      Phys Life Rev. 2017 Dec;22-23:88-119. (PMID: 28688729)
      Biophys J. 2011 Dec 21;101(12):2919-28. (PMID: 22208190)
      Cancer Cell. 2005 Sep;8(3):241-54. (PMID: 16169468)
      Curr Opin Cell Biol. 2006 Oct;18(5):579-86. (PMID: 16904883)
      Science. 2003 May 2;300(5620):795-8. (PMID: 12730600)
      Bioessays. 2017 Jan;39(1):1-12. (PMID: 27930828)
      Proc Natl Acad Sci U S A. 2018 Feb 6;115(6):1192-1197. (PMID: 29358406)
      Cell Death Dis. 2019 Jun 7;10(6):452. (PMID: 31175271)
      Nat Rev Mol Cell Biol. 2013 Aug;14(8):503-17. (PMID: 23860236)
      Nat Cell Biol. 2008 Sep;10(9):1039-50. (PMID: 19160484)
      Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16245-50. (PMID: 19805288)
      Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19372-7. (PMID: 24222685)
    • Grant Information:
      K25 HL079165 United States HL NHLBI NIH HHS; R01 HL109505 United States HL NHLBI NIH HHS; R44 HL139248 United States HL NHLBI NIH HHS; U01 EB016422 United States EB NIBIB NIH HHS
    • Accession Number:
      0 (Integrins)
      EC 2.7.10.2 (Focal Adhesion Kinase 1)
      EC 2.7.10.2 (PTK2 protein, human)
    • Publication Date:
      Date Created: 20200318 Date Completed: 20201112 Latest Revision: 20230929
    • Publication Date:
      20230929
    • Accession Number:
      PMC7056303
    • Accession Number:
      10.1126/sciadv.aax1909
    • Accession Number:
      32181337