Refereed journal article or data article (A1)

Myosin-X and talin modulate integrin activity at filopodia tips




List of Authors: Miihkinen Mitro, Grönloh Max L. B., Popovic Ana, Vihinen Helena, Jokitalo Eija, Goult Benjamin T., Ivaska Johanna, Jacquemet Guillaume

Publisher: CELL PRESS

Publication year: 2021

Journal: Cell Reports

Journal name in source: CELL REPORTS

Journal acronym: CELL REP

Volume number: 36

Issue number: 11

Number of pages: 23

ISSN: 2211-1247

eISSN: 2211-1247

DOI: http://dx.doi.org/10.1016/j.celrep.2021.109716

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/67259507


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 b1-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.

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Last updated on 2022-07-04 at 18:36