| First Author | Liao Z | Year | 2017 |
| Journal | J Cell Sci | Volume | 130 |
| Issue | 20 | Pages | 3532-3541 |
| PubMed ID | 28864764 | Mgi Jnum | J:315606 |
| Mgi Id | MGI:6829368 | Doi | 10.1242/jcs.205203 |
| Citation | Liao Z, et al. (2017) Optogenetic interrogation of integrin alphaVbeta3 function in endothelial cells. J Cell Sci 130(20):3532-3541 |
| abstractText | The integrin alphaVbeta3 is reported to promote angiogenesis in some model systems but not in others. Here, we used optogenetics to study the effects of alphaVbeta3 interaction with the intracellular adapter kindlin-2 (Fermt2) on endothelial cell functions potentially relevant to angiogenesis. Because interaction of kindlin-2 with alphaVbeta3 requires the C-terminal three residues of the beta3 cytoplasmic tail (Arg-Gly-Thr; RGT), optogenetic probes LOVpep and ePDZ1 were fused to beta3DeltaRGT-GFP and mCherry-kindlin-2, respectively, and expressed in beta3 integrin-null microvascular endothelial cells. Exposure of the cells to 450 nm (blue) light caused rapid and specific interaction of kindlin-2 with alphaVbeta3 as assessed by immunofluorescence and total internal reflection fluorescence (TIRF) microscopy, and it led to increased endothelial cell migration, podosome formation and angiogenic sprouting. Analyses of kindlin-2 mutants indicated that interaction of kindlin-2 with other kindlin-2 binding partners, including c-Src, actin, integrin-linked kinase and phosphoinositides, were also likely necessary for these endothelial cell responses. Thus, kindlin-2 promotes alphaVbeta3-dependent angiogenic functions of endothelial cells through its simultaneous interactions with beta3 integrin and several other binding partners. Optogenetic approaches should find further use in clarifying spatiotemporal aspects of vascular cell biology. |
