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Myosin-X and talin modulate integrin activity at filopodia tips

Authors :
Guillaume Jacquemet
Mitro Miihkinen
Eija Jokitalo
Johanna Ivaska
Helena Vihinen
Benjamin T. Goult
Max L.B. Grönloh
Institute of Biotechnology
Electron Microscopy
University Management
Source :
Cell Reports, Cell Reports, Vol 36, Iss 11, Pp 109716-(2021)
Publication Year :
2021
Publisher :
Elsevier, 2021.

Abstract

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.<br />Graphical abstract<br />Highlights • Integrin activity is spatially regulated in filopodia • Integrin activation at filopodia tips is regulated by talin and MYO10 • MYO10 is required to activate (but not transport) integrins at filopodia tips • We propose a two-step integrin activation model in filopodia<br />Cells utilize cellular protrusions such as filopodia to explore their environment as they migrate. Filopodia assemble unique integrin-adhesion complexes to sense the extracellular matrix. Miihkinen et al. show that MYO10 and talin regulate integrin activity at filopodia tips and propose a two-step integrin activation model in filopodia.

Details

Language :
English
ISSN :
22111247
Database :
OpenAIRE
Journal :
Cell Reports, Cell Reports, Vol 36, Iss 11, Pp 109716-(2021)
Accession number :
edsair.doi.dedup.....5aac38f64c4800b48c76cc3d09ea0a8c