In:
Journal of Cell Science, The Company of Biologists
Abstract:
Dynamic regulation of cell-cell adhesion by the coordinated formation and dissolution of E–Cadherin-based adherens junctions (AJs) is critical for tissue homeostasis. The actin-binding protein Cortactin interacts with E-Cadherin and enables F-actin accumulation at AJs. We here were interested to study broader functional interactions of Cortactin in adhesion complexes. In line with literature, we demonstrate that Cortactin binds to E-Cadherin and a posttranslational modification of Cortactin, RhoA–induced phosphorylation by PKD1 at S298, impairs AJ assembly and supports their dissolution. Two novel S298-phosphorylation-dependent interactions were identified: Phosphorylation of Cortactin decreases its interaction with beta-Catenin and the actin-binding protein Vinculin. Secondly, binding of Vinculin to beta-Catenin as well as linkage of Vinculin to F-actin are also significantly compromised. Accordingly, we found that regulation of cell-cell adhesion by phosphorylation of Cortactin downstream of RhoA/PKD1 is vitally dependent on Vinculin–mediated protein interactions. Thus, Cortactin unexpectedly is an important integration node for the dynamic regulation of protein complexes during breakdown and formation of AJs.
Type of Medium:
Online Resource
ISSN:
1477-9137
,
0021-9533
Language:
English
Publisher:
The Company of Biologists
Publication Date:
2016
detail.hit.zdb_id:
219171-4
detail.hit.zdb_id:
1483099-1
SSG:
12
