Miller Lab: Vinculin maintains junction integrity and barrier function at epithelial tricellular junctions

Epithelial cells must adhere to one another to create a barrier that is essential during development and as cells divide and for preventing pathogen invasion or diseases such as inflammatory bowel disease.

Vinculin is a mechanosensitive protein – meaning that it can be recruited to cellular adhesion complexes under force. Prior studies have focused on Vinculin’s role in mechanosensitively strengthening cell-substrate adhesion or in cell-cell junction reinforcement at simple epithelial interfaces where only two cells touch. By contrast, much less is known about how more complex tricellular junctions (TCJs) (the points where three cells meet) are maintained or reinforced when mechanical force is applied on tissues.

In this paper, using the embryonic epithelium of Xenopus laevis (frog) embryos as a model, the Miller lab defines a mechanism by which the mechanosensitive protein Vinculin helps anchor the network of actin cytoskeleton proteins at tricellular junctions, thus maintaining TCJ integrity and barrier function.

The authors were able to show the importance of Vinculin by generating frog embryos where the Vinculin protein was depleted. When they increased tension on the tissues of these embryos, they detected disruptions in the cell junctions. The authors used innovative techniques to apply tension on the embryonic epithelium and to measure leaks in barrier function. In the embryos with reduced levels of Vinculin, the researchers detected more barrier leaks – specifically at the tricellular junctions.

“Vinculin’s ability to be mechanosensitively recruited to TCJs under increased mechanical force may be especially important in dynamic epithelial tissues that need to tune their adhesion and maintain overall barrier function during developmental morphogenesis or in adult epithelial tissues that experience high mechanical forces,” the authors write.

Authors of the paper are Dr. Lotte van den Goor [Miller lab graduate student (PhD, 2023) now a postdoctoral fellow at Johns Hopkins]; Jolene Iseler [Miller lab undergrad (BS 2023), now a graduate student at Dartmouth]; Katherine Koning [Miller lab graduate student in the Cellular and Molecular Biology Graduate Program], and MCDB Professor Ann Miller.