Abstract

Talin, the primary link between the ECM-binding integrin receptors and the actin cytoskeleton, serves as a mechanosensitive signaling hub as its 13 force-dependent binary switch domains convert mechanical signals into biological signals by spatially localizing numerous signaling proteins in space and time to control signaling outputs. I will discuss how the mechanical signaling through talin represents a highly sophisticated machinery for controlling enzymatic processes. I will focus on the enzymes that interact directly with talin, including CDK1 and PKA, as well as presenting new unpublished data on CDKL5 and Src binding directly to talin, as each serves as a paradigm for a different mechanism for how mechanical signals can alter enzymatic signaling. I will discuss how understanding the different modes of scaffolding of each of these enzymes has enabled us to establish design principles of mechanically operated enzymes.

Bio

Professor Ben Goult is a structural mechanobiologist whose work combines structural biology, biochemistry, biophysics and mechanobiology to define the role of how physical and mechanical forces are sensed by cells to control cellular processes. After a PhD at UMIST and industry work at AstraZeneca, he returned to academia in 2006 to study the protein talin, first at the University of Leicester, then leading his own lab at Kent (2014), and now as Professor at Liverpool (2024). Ben is recognized for defining the protein talin as a major mechanosensitive signaling hub, and more recently discovered that talin has “molecular memory” providing organisms with the capability to store data through persistent alterations in protein conformation. His foundational work on talin has shown that mechanosensitive proteins containing force-dependent binary switches are able to store binary information persistently, which can be written/updated using small changes in mechanical force.