Deciphering the mechanisms of talin directing cell adhesion and signaling

Talin plays a pivotal role in forming multicellular tissues, governing crucial cellular functions such as adhesion and motility, which are implicated in various human diseases. By coordinating the recruitment of essential regulatory elements at focal adhesions, talin facilitates their formation and influences cytoskeletal dynamics, profoundly impacting cell adhesion mechanisms. This project seeks to discover how the structural properties and post-translational modifications affect the function of talin. This project will determine near-atomic resolution cryogenic electron microscopy structures of talin in its phosphorylated active state and its interaction with F-actin. Biochemical assays and live cell experiments will yield a comprehensive understanding of the function of talin in cellular adhesion processes. The PI is deeply committed to outreach activities to foster scientific curiosity and learning among younger students. This project will strive to inspire the next generation of scientists through workshops, mentorship programs, and involvement in science fairs. Talin occupies a central position in cell adhesion, primarily by activating integrins into high affinity states and facilitating the connection between integrins and the cytoskeleton. This research project will use the first Japan Electron Optics Laboratory (JEOL) 300 kV cryogenic Atomic Resolution Microscope (cryoARM300) installed in the US to determine the near-atomic resolution structures of talin. The actin-bound form of talin and its effects in the regulation of adhesion dynamics in live cells will be determined. This project will also determine near-atomic resolution cryoEM structures of talin in its phosphorylated active state and complement the data with biochemical and in live cell experiments. Thus, significant mechanistic insights into cell adhesion will be obtained on a new cryo-electron microscope in the US that has aided near-atomic resolution insights into many biological processes. This project is supported by the Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.