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Myosin-X and talin modulate integrin activity at filopodia tips
- 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.
- Subjects :
- Talin
MECHANISM
DYNAMICS
UP-REGULATION
MYO10
Extracellular matrix
ACTIVATION
0302 clinical medicine
RNA interference
Myosin
Pseudopodia
Biology (General)
RNA, Small Interfering
Receptor
Filopodia
0303 health sciences
biology
FERM domain
Chemistry
Integrin beta1
Cell biology
CONFORMATION
adhesion
embryonic structures
RNA Interference
CELL-ADHESION
Protein Binding
animal structures
QH301-705.5
CARGO RECOGNITION
Integrin
macromolecular substances
Myosins
Article
03 medical and health sciences
Protein Domains
Cell Line, Tumor
REVEALS
Humans
integrin activity
QH581.2
030304 developmental biology
Focal Adhesions
Binding Sites
COMPLEX
ELONGATION
Activator (genetics)
fungi
biology.protein
1182 Biochemistry, cell and molecular biology
030217 neurology & neurosurgery
Subjects
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