Journal
DEVELOPMENTAL CELL
Volume 34, Issue 4, Pages 475-483Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2015.06.015
Keywords
-
Categories
Funding
- DFG [GR2111/2-2]
- Wilhelm Sander Stiftung [2013.149.1]
- Deutsche Krebshilfe [109550]
- Academy of Finland ERC
- Sigrid Juselius Foundation
- Finnish Cancer Organization
Ask authors/readers for more resources
Regulated turnover of integrin receptors is essential for cell adhesion and migration. Pathways selectively regulating beta 1-integrin recycling are implicated in cancer invasion and metastasis, yet proteins required for the internalization of this pro-invasive integrin remain to be identified. Here, we uncover formin-like 2 (FMNL2) as a critical regulator of beta 1-integrin internalization downstream of protein kinase C (PKC). PKC alpha associates with and phosphorylates FMNL2 at S1072 within its Diaphanous autoregulatory region, leading to the release of formin autoinhibition. Phosphorylation of FMNL2 triggers its rapid relocation and promotes its interaction with the cytoplasmic tails of the a-integrin subunits for beta 1-integrin endocytosis. FMNL2 drives beta 1-integrin internalization and invasive motility in a phosphorylationdependent manner, while a FMNL2 mutant defective in actin assembly interferes with beta 1-integrin endocytosis and cancer cell invasion. Our data establish a role for FMNL2 in the regulation of beta 1-integrin and provide a mechanistic understanding of the function of FMNL2 in cancer invasiveness.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available