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Coupling integrin dynamics to cellular adhesion behaviors
Visualizing fluorescent proteins is essential for understanding cellular function. While advances in microscopy can now resolve individual molecules, determining whether the labeled molecules report native behaviors and how the measured behaviors can be coupled to cellular outputs remains challengin...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124568/ https://www.ncbi.nlm.nih.gov/pubmed/30111545 http://dx.doi.org/10.1242/bio.036806 |
Sumario: | Visualizing fluorescent proteins is essential for understanding cellular function. While advances in microscopy can now resolve individual molecules, determining whether the labeled molecules report native behaviors and how the measured behaviors can be coupled to cellular outputs remains challenging. Here, we used integrin alpha-beta heterodimers – which connect extracellular matrix (ECM) and the cytoskeleton – to quantify the mobility and conformation of labeled integrins. We found that while unlabeled and labeled integrins all localized to adhesions and support anchorage-dependent cell function, integrin mobility decreased when the beta rather than the alpha subunit was labeled. In contrast to unlabeled and alpha labeled subunits, beta labeled subunits changed cellular behavior; decreasing protrusive activity and increasing adhesion size and the extent of cell spreading. Labeling the beta subunit changed the integrin conformation, extending the molecule and exposing an epitope that is revealed by activation with Mn(2+) treatment. Our findings indicate labeling induced changes in dynamic integrin behavior alter molecular conformation as well as cellular adhesion-dependent function to demonstrate a coupling between molecular inputs and distinct cellular outputs. This article has an associated First Person interview with the first author of the paper. |
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