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Miihkinen M, Grönloh MLB, Popović A, et al. Myosin-X and talin modulate integrin activity at filopodia tips. Cell Rep. 2021;36(11):109716doi: 10.1016/j.celrep.2021.109716.
Miihkinen, M., Grönloh, M. L. B., Popović, A., Vihinen, H., Jokitalo, E., Goult, B. T., Ivaska, J., & Jacquemet, G. (2021). Myosin-X and talin modulate integrin activity at filopodia tips. Cell reports, 36(11), 109716. https://doi.org/10.1016/j.celrep.2021.109716
Miihkinen, Mitro, et al. "Myosin-X and talin modulate integrin activity at filopodia tips." Cell reports vol. 36,11 (2021): 109716. doi: https://doi.org/10.1016/j.celrep.2021.109716
Miihkinen M, Grönloh MLB, Popović A, Vihinen H, Jokitalo E, Goult BT, Ivaska J, Jacquemet G. Myosin-X and talin modulate integrin activity at filopodia tips. Cell Rep. 2021 Sep 14;36(11):109716. doi: 10.1016/j.celrep.2021.109716. PMID: 34525374; PMCID: PMC8456781.
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Cell Rep. 2021 Sep 14;36(11):109716. doi: 10.1016/j.celrep.2021.109716.

Myosin-X and talin modulate integrin activity at filopodia tips.

Cell reports

Mitro Miihkinen, Max L B Grönloh, Ana Popović, Helena Vihinen, Eija Jokitalo, Benjamin T Goult, Johanna Ivaska, Guillaume Jacquemet

Affiliations

  1. Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland.
  2. Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20520 Turku, Finland.
  3. Electron Microscopy Unit, Institute of Biotechnology, University of Helsinki, 00790 Helsinki, Finland.
  4. School of Biosciences, University of Kent, Canterbury, CT2 7NJ Kent, UK.
  5. Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; Department of Life Technologies, University of Turku, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland. Electronic address: [email protected].
  6. Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20520 Turku, Finland; Turku Bioimaging, University of Turku and Åbo Akademi University, 20520 Turku, Finland. Electronic address: [email protected].

PMID: 34525374 PMCID: PMC8456781 DOI: 10.1016/j.celrep.2021.109716

Abstract

Filopodia assemble unique integrin-adhesion complexes to sense the extracellular matrix. However, the mechanisms of integrin regulation in filopodia are poorly defined. Here, we report that active integrins accumulate at the tip of myosin-X (MYO10)-positive filopodia, while inactive integrins are uniformly distributed. We identify talin and MYO10 as the principal integrin activators in filopodia. In addition, deletion of MYO10's FERM domain, or mutation of its β1-integrin-binding residues, reveals MYO10 as facilitating integrin activation, but not transport, in filopodia. However, MYO10's isolated FERM domain alone cannot activate integrins, potentially because of binding to both integrin tails. Finally, because a chimera construct generated by swapping MYO10-FERM by talin-FERM enables integrin activation in filopodia, our data indicate that an integrin-binding FERM domain coupled to a myosin motor is a core requirement for integrin activation in filopodia. Therefore, we propose a two-step integrin activation model in filopodia: receptor tethering by MYO10 followed by talin-mediated integrin activation.

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Keywords: Filopodia; MYO10; adhesion; integrin activity; talin

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

References

  1. Methods. 2017 Feb 15;115:80-90 - PubMed
  2. Structure. 2010 Oct 13;18(10):1289-99 - PubMed
  3. PLoS One. 2014 Sep 17;9(9):e107097 - PubMed
  4. Elife. 2016 Jan 27;5:e10130 - PubMed
  5. J Cell Biol. 2010 May 3;189(3):541-56 - PubMed
  6. J Biol Chem. 2010 Jun 18;285(25):19605-14 - PubMed
  7. J Cell Biol. 2015 Sep 14;210(6):1013-31 - PubMed
  8. Semin Cell Dev Biol. 2020 Jun;102:81-89 - PubMed
  9. J Cell Sci. 2018 Aug 20;132(4): - PubMed
  10. Nat Rev Mol Cell Biol. 2013 Jul;14(7):430-42 - PubMed
  11. Cancer Discov. 2012 Aug;2(8):706-21 - PubMed
  12. J Cell Sci. 2009 Jan 15;122(Pt 2):165-70 - PubMed
  13. Nat Commun. 2019 Aug 9;10(1):3593 - PubMed
  14. Nat Cell Biol. 2017 Apr;19(4):292-305 - PubMed
  15. Nat Struct Mol Biol. 2016 Feb;23(2):172-9 - PubMed
  16. Nat Commun. 2015 Feb 13;6:6265 - PubMed
  17. Nat Commun. 2015 Sep 30;6:8492 - PubMed
  18. Biochem Biophys Res Commun. 2004 Jun 18;319(1):214-20 - PubMed
  19. Proc Natl Acad Sci U S A. 2020 Dec 22;117(51):32402-32412 - PubMed
  20. J Clin Invest. 2014 Mar;124(3):1069-82 - PubMed
  21. Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):10339-10344 - PubMed
  22. Essays Biochem. 2019 Oct 31;63(5):535-551 - PubMed
  23. J Cell Sci. 2010 Oct 15;123(Pt 20):3525-34 - PubMed
  24. EMBO J. 2009 Nov 18;28(22):3623-32 - PubMed
  25. Cell Rep. 2018 Nov 27;25(9):2401-2416.e5 - PubMed
  26. Nat Methods. 2012 Jun 28;9(7):676-82 - PubMed
  27. Nat Commun. 2016 Dec 02;7:13297 - PubMed
  28. Bio Protoc. 2017 Dec 20;7(24): - PubMed
  29. J Cell Sci. 2018 Oct 29;131(21): - PubMed
  30. Mol Biol Cell. 2021 Mar 15;32(6):470-474 - PubMed
  31. Nat Cell Biol. 2019 Jan;21(1):25-31 - PubMed
  32. Nat Struct Mol Biol. 2015 May;22(5):383-9 - PubMed
  33. J Cell Biol. 2017 Oct 2;216(10):3387-3403 - PubMed
  34. J Cell Sci. 2018 Jun 15;131(12): - PubMed
  35. J Cell Biol. 2020 Jun 1;219(6): - PubMed
  36. Nat Cell Biol. 2002 Mar;4(3):246-50 - PubMed
  37. Proc Natl Acad Sci U S A. 2019 Oct 29;116(44):22196-22204 - PubMed
  38. Sci Rep. 2017 Apr 13;7:46233 - PubMed
  39. Nat Cell Biol. 2015 Nov;17(11):1412-21 - PubMed
  40. J Cell Sci. 2013 Oct 15;126(Pt 20):4756-68 - PubMed
  41. Nano Lett. 2020 Apr 8;20(4):2230-2245 - PubMed
  42. Cancers (Basel). 2019 May 02;11(5): - PubMed
  43. Curr Biol. 2009 Jun 9;19(11):967-73 - PubMed
  44. Curr Biol. 2019 Jan 21;29(2):202-216.e7 - PubMed
  45. Nat Methods. 2017 Jan;14(1):53-56 - PubMed
  46. J Biol Chem. 2009 May 29;284(22):15097-106 - PubMed
  47. J Biol Chem. 2007 Feb 2;282(5):3205-12 - PubMed
  48. J Cell Biol. 2005 Aug 15;170(4):619-26 - PubMed
  49. EMBO J. 2011 Jun 03;30(13):2734-47 - PubMed
  50. Nucleic Acids Res. 2018 Jul 2;46(W1):W296-W303 - PubMed
  51. Nat Cell Biol. 2004 Jun;6(6):523-31 - PubMed
  52. Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18928-33 - PubMed
  53. J Cell Sci. 2009 Nov 15;122(Pt 22):4009-11 - PubMed
  54. J Cell Biol. 2013 Sep 16;202(6):917-35 - PubMed
  55. EMBO J. 2010 Mar 17;29(6):1069-80 - PubMed
  56. J Cell Biol. 2018 Sep 3;217(9):3203-3218 - PubMed
  57. J Cell Biol. 2006 Jun 5;173(5):767-80 - PubMed
  58. Curr Opin Cell Biol. 2015 Oct;36:23-31 - PubMed
  59. Eur J Cell Biol. 2010 Sep;89(9):661-73 - PubMed
  60. PLoS Biol. 2019 Mar 27;17(3):e3000202 - PubMed
  61. Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3572-7 - PubMed
  62. Nat Rev Mol Cell Biol. 2008 Jun;9(6):446-54 - PubMed

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