Myosin-X and talin modulate integrin activity at filopodia tips
Mitro Miihkinen,
Max L.B. Grönloh,
Ana Popović,
Helena Vihinen,
Eija Jokitalo,
Benjamin T. Goult,
Johanna Ivaska,
Guillaume Jacquemet
Affiliations
Mitro Miihkinen
Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland
Max L.B. Grönloh
Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland
Ana Popović
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
Helena Vihinen
Electron Microscopy Unit, Institute of Biotechnology, University of Helsinki, 00790 Helsinki, Finland
Eija Jokitalo
Electron Microscopy Unit, Institute of Biotechnology, University of Helsinki, 00790 Helsinki, Finland
Benjamin T. Goult
School of Biosciences, University of Kent, Canterbury, CT2 7NJ Kent, UK
Johanna Ivaska
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; Corresponding author
Guillaume Jacquemet
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; Corresponding author
Summary: 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.
