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A novel, matrix-specific GEF/GAP interaction regulates Rho GTPase crosstalk critical for 3D collagen migration
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kutys, Matthew L. |
| Copyright Year | 2014 |
| Abstract | Matthew L. Kutys: A novel, matrix-specific GEF/GAP interaction regulates Rho GTPase crosstalk critical for 3D collagen migration (Under the direction of Kenneth M. Yamada) Differential activation of the Rho family GTPases, Cdc42, Rac1, and RhoA, helps to govern the distinct morphological and migratory phenotypes downstream of adhesion to different extracellular matrix (ECM) proteins. However, it is not known how specific GTPase-dependent signaling pathways are activated in response to different ECM ligands. We hypothesized that adhesion to different ECM molecules, such as collagen and fibronectin, will trigger selective regulation of guanine nucleotide exchange factors (GEFs) to regulate the appropriate matrix-specific cell migratory response. We utilized an affinity precipitation-based mass spectrometry screen to isolate active GEFs from primary human fibroblasts migrating in collagen, fibronectin, or ECM-free environments. Among the GEFs identified, we found that βPix, a Rac1/Cdc42 GEF, was robustly activated only during migration in collagen matrices. Knockdown of βPix led to a collagen-specific migration defect characterized by rapid, spatially-deregulated protrusions, rounded morphology, the absence of stable leading and trailing edges, and robust contraction of the adjacent collagen matrix. In contrast to fibroblasts migrating on fibronectin, βPix in cells migrating in collagen did not localize to focal adhesions, but instead transiently accumulated on the membrane adjacent to areas of cellular protrusion as determined by live cell imaging, immunofluorescence staining, and biochemical |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://cdr.lib.unc.edu/indexablecontent/uuid:bf6d58e1-869c-49e5-baff-5df0a348eaec?dl=true |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
