Force tuning through regulation of clathrin-dependent integrin endocytosis.
J Cell Biol
; 222(1)2023 01 02.
Article
in En
| MEDLINE
| ID: mdl-36250940
ABSTRACT
Integrin endocytosis is essential for many fundamental cellular processes. Whether and how the internalization impacts cellular mechanics remains elusive. Whereas previous studies reported the contribution of the integrin activator, talin, in force development, the involvement of inhibitors is less documented. We identified ICAP-1 as an integrin inhibitor involved in mechanotransduction by co-working with NME2 to control clathrin-mediated endocytosis of integrins at the edge of focal adhesions (FA). Loss of ICAP-1 enables ß3-integrin-mediated force generation independently of ß1 integrin. ß3-integrin-mediated forces were associated with a decrease in ß3 integrin dynamics stemming from their reduced diffusion within adhesion sites and slow turnover of FA. The decrease in ß3 integrin dynamics correlated with a defect in integrin endocytosis. ICAP-1 acts as an adaptor for clathrin-dependent endocytosis of integrins. ICAP-1 controls integrin endocytosis by interacting with NME2, a key regulator of dynamin-dependent clathrin-coated pits fission. Control of clathrin-mediated integrin endocytosis by an inhibitor is an unprecedented mechanism to tune forces at FA.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Clathrin
/
Integrin beta1
/
Focal Adhesions
/
Integrin beta3
/
Endocytosis
Language:
En
Journal:
J Cell Biol
Year:
2023
Document type:
Article
Affiliation country: