Journal
BIOLOGY OPEN
Volume 5, Issue 4, Pages 499-506Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/bio.016428
Keywords
Tensin 1; P130Cas; Actin cytoskeleton; Cell migration; Focal adhesion
Categories
Funding
- Biomedical Research Council [R-154-000-423-305]
- Mechanobiology Institute, Singapore [R-714-004-007-271]
- Grants-in-Aid for Scientific Research [26560410, 15H04966, 15H01820, 15H06770] Funding Source: KAKEN
Ask authors/readers for more resources
Cell migration is a highly dynamic process that plays pivotal roles in both physiological and pathological processes. We have previously reported that p130Cas supports cell migration through the binding to Src as well as phosphorylation-dependent association with actin retrograde flow at focal adhesions. However, it remains elusive how phosphorylated Cas interacts with actin cytoskeletons. We observe that the actin-binding protein, tensin 1, co-localizes with Cas, but not with its phosphorylation-defective mutant, at focal adhesions in leading regions of migrating cells. While a truncation mutant of tensin 1 that lacks the phosphotyrosine-binding PTB and SH2 domains (tensin 1-SH2PTB) poorly co-localizes or co-immunoprecitates with Cas, bacterially expressed recombinant tensin 1-SH2PTB protein binds to Cas in vitro in a Cas phosphorylation-dependent manner. Furthermore, exogenous expression of tensin 1-SH2PTB, which is devoid of the actin-interacting motifs, interferes with the Cas-driven cell migration, slows down the inward flux of Cas molecules, and impedes the displacement of Cas molecules from focal adhesions. Taken together, our results show that tensin 1 links inwardly moving actin cytoskeletons to phosphorylated Cas at focal adhesions, thereby driving cell migration.
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