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

Miihkinen, Mitro ORCID: 0000-0001-6822-3647, Grönloh, Max LB ORCID: 0000-0003-0109-8225, Popović, Ana ORCID: 0000-0003-2981-0093, Vihinen, Helena ORCID: 0000-0003-3862-9237, Jokitalo, Eija ORCID: 0000-0002-4159-6934, Goult, Benjamin T ORCID: 0000-0002-3438-2807, Ivaska, Johanna ORCID: 0000-0002-6295-6556 and Jacquemet, Guillaume ORCID: 0000-0002-9286-920X (2021) Myosin-X and talin modulate integrin activity at filopodia tips. Cell reports, 36 (11). 109716-.

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Official URL: http://dx.doi.org/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.

Item Type:	Article
Uncontrolled Keywords:	Cell Line, Tumor, Focal Adhesions, Pseudopodia, Humans, Myosins, Talin, RNA, Small Interfering, RNA Interference, Binding Sites, Protein Binding, Protein Domains, Integrin beta1
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	13 Mar 2024 10:01
Last Modified:	15 Mar 2024 20:51
DOI:	10.1016/j.celrep.2021.109716
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179305