More about Integrins and Cadherin Signaling

Day 1 continued with a talk by Bernard Wehrle-Haller. Beautiful work, addressing important questions about integrin biology. Noteworthy was the differences of the different integrin isoforms. The muscle isoform does not recruit Paxillin as efficiently as the isoform expressed in the fibroblasts. This suggests that it perhaps does not signal but is an efficient machine to provide attachment to the musculature. This demonstrates how the body makes small changes in its toolbox to adapt to vastly different needs. Another tool in the tool kit to regulate integrin function is via acetylation. They demonstrate that de-acetylated integrins are actually much more stable in an adhesion, wherein the recovery of these integrins upon FRAP was very slow compared to the integrins that are normally processed. This suggests many ways of regulating integrin function to adapt to the adhesions. I was amazed at how many unknowns are still there in integrin biology even after a massive body of understanding of focal adhesions on glass.

We switched from integrins to cadherins. Talk by Vania Braga from Imperial College London, was very interesting where she talked about their novel insights into how epithelial cell-cell adhesions form. She showed us the presence of two populations of actin – the junctional actin present at the junction and marked by overlap with the Ecadherin staining and the thin bundles present close to the junction. Unlike junctional actin, thin bundles exist even when cells do not form cell-cell junctions. They developed an automated platform to perform a genome wide RNAi screen to identify factors that regulate one or the other actin pools. One interesting factor they identified was EEF1A, which has a traditionally defined role in mRNA translation. This led to a 50% increase in the level of Ecadherin at the junctions without an increase in the overall levels of Ecadherin, demonstrating a probable existence of a moonlighting function of EEF1A. Wow, the traditional nomenclature does make us think that it would have only one function, in the omics era, a lot of this might change. When I chatted with Professor Braga later, she revealed that there is some old literature, which shows that EEF1A binds to actin, which needs to be revisited to understand junction formation. In the next part of her talk she showed that cortical tension also modulated junctions. They modulated cortical tension by presenting cells with substrates varying in geometry. What they found that lower tension leads to an increased number of cell-cell contacts whereas an increase in the same leads to more straight (a possible ready of tension bearing junctions) junctions.

Wow, lots of information of new tools and ways to think about cell-cell and cell-matrix adhesions.

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