Cell Signaling | Cell Adhesion | Cytoskeleton
The focal adhesion anchoring domains of p130Cas regulate pro-motile signalling
Dominique Donato*, Larisa Ryzhova, Leslie Meenderink, Irina Kaverina, Steve Hanks
*Corresponding author: Dominique Donato
Physics of Life Processes, Leiden Institute of Physics, Leiden University, , Netherlands
Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA
F1000Posters 2011, 2: 231 (poster) [ENGLISH]
Poster [3.58 MB]
Biochemical Society/Wellcome Trust Focused Meeting 2011 - Cellular cytoskeletal motor proteins , 30 Mar - 1 Apr 2011, P035
The Src substrate, p130Cas, has been linked to pro-motile signalling and mechanosensing. Central to its ability to promote pro-motile signalling is the need for p130Cas to become localized to focal adhesions (FAs). These FAs serve as a link between the extracellular matrix and the cytoskeleton.
Using live cell total internal reflection fluorescence microscopy, we found that p130Cas localizes to FAs throughout their lifetime and disassembles slowly at these sites. Additionally, p130Cas has a high mobile fraction, explaining previous observations of highly transient tyrosine phosphorylation. Imaging of Cas
/ mouse embryonic fibroblasts (MEFs) reconstituted with fluorescent variants of p130Cas demonstrated a need for both the Src homology 3 (SH3) and Cas-family C-terminal Homology (CCH) domains in recruiting p130Cas to these sites.
Additional experiments illustrated that FAK is the SH3-binding partner responsible for targeting p130Cas to FAs through the SH3 domain.
We illustrated for the first time that the CCH domain has a signalling function, as deletion of this domain led to reduced p130Cas signalling and cell motility. These results illustrate the functional importance of the SH3 and CCH domains in anchoring p130Cas to focal adhesions <a target=”_blank” href=http://www.ncbi.nlm.nih.gov/pubmed/20430882> Donato et al 2010.
No relevant conflicts of interest declared.
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