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Discovery of the role of formins and myosin IIA motor proteins in the regulation of the mechanosensory function of filopodia

  • Date: 2022
  • Institution: Shenzhen Bay Laboratory (China), Mechanobiology Institute (Singapore)
  • Authors: Artem K. Efremov, Mingxi Yao, Yuze Sun, Yee Han Tee, Michael P. Sheetz, Alexander D. Bershadsky, Boris Martinac, Jie Yan
  • Aim of study: The process of cell migration plays the central role in the development and maintenance of multicellular organisms. To guide their motion through extracellular matrix (ECM), living cells use dynamic membrane projections known as filopodia, which are responsible for sensing of the surrounding microenvironment and formation of initial adhesion contacts with ECM. To this aim, filopodia probe mechanical properties of ECM. Although the major proteins contributing to the filopodia formation, growth and adhesion have been previously identified, there is still a large gap in understanding of the molecular mechanisms underlying the mechanosensory function of filopodia. To study them, I, together with the group of Alexander Bershadsky, investigated the role of mechanical forces in the regulation of the dynamic and adhesive properties of filopodia.

Major results: Individual filopodia have been shown to be highly sensitive to the local application of mechanical forces, which appear to induce filopodia growth in HeLa cancer cells. Mor importantly, it has been found that mechanical forces generated by myosin IIA proteins at the filopodia bases can be effectively transmitted over large distances by the actin cytoskeleton to the filopodia tips, where they participate in the regulation of mechano-sensing protein complexes responsible for filopodia growth and adhesion. Inhibition of myosin II or the formin-mediated association between actin filaments and the filopodia tips resulted in filopodia that are unable to form stable adhesions with the extracellular matrix, suggesting that these proteins play a major role in the mechanosensory function of filopodia.

Contribution to the research field: It was shown that myosin IIA and formins play the central role in the regulation of the mechanosensitive behaviour of filopodia, explaining previously reported mechano-dependent guidance of the neurite growth cone pathfinding by filopodia. The corresponding publication of our team was recommended by F1000 faculty group.