Rho GTPases and actomyosin: Partners in regulating epithelial cell-cell junction structure and function

Abstract

Epithelial tissues are defined by polarized epithelial cells that are integrated into tissues and exhibit barrier function in order to regulate what is allowed to pass between cells. Cell-cell junctions must be stable enough to promote barrier function and tissue integrity, yet plastic enough to remodel when necessary. This remarkable ability to dynamically sense and respond to changes in cell shape and tissue tension allows cell-cell junctions to remain functional during events that disrupt epithelial homeostasis including morphogenesis, wound healing, and cell division. In order to achieve this plasticity, both tight junctions and adherens junctions are coupled to the underlying actomyosin cytoskeleton. Here, we discuss the importance of the junctional linkage to actomyosin and how a localized zone of active RhoA along with other Rho GTPases work together to orchestrate junctional actomyosin dynamics. We focus on how scaffold proteins help coordinate Rho GTPases, their upstream regulators, and their downstream effectors for efficient, localized Rho GTPase signaling output. Additionally, we highlight important roles junctional actin-binding proteins play in addition to their traditional roles in organizing actin. Together, Rho GTPases, their regulators, and effectors form compartmentalized signaling modules that regulate actomyosin structure and contractility to achieve proper cell-cell adhesion and tissue barriers.

Proteomic Analysis of Stromal and Epithelial Cell Communications in Human Endometrial Cancer Using a Unique 3D Co‐Culture Model

“…Earlier studies have shown that RhoA signaling has a crucial role in tumor cell proliferation and metastasis . Our proteomics data identified ARPC2, ARPC3, MSN, and PPP1R12A involvement in RhoA signaling and these proteins achieve the proper cell–cell adhesion and tissue barriers via regulating actomyosin structure . Interestingly, PPP1R12A was one that had similar expression profile in our cancer co‐culture model as well as in human patient endometrial cancer, and this data is being supported by Human Protein Atlas Database .…”

The Hippo pathway effector Taz is required for cell fate specification and fertilization in zebrafish

“…Adherens and tight junctions associate with the actomyosin cytoskeleton (reviewed in Arnold et al, 2017;Quiros and Nusrat, 2014). As described above, actin was strongly enriched at the MC-oocyte contact point from early stage III onward ( Fig.…”

Potential Regulatory Effects of Corticotropin-Releasing Factor on Tight Junction-Related Intestinal Epithelial Permeability are Partially Mediated by CK8 Upregulation

“…It interacts with GTP to activate downstream effectors and participates in F-actin recombination in the cytoskeleton and influences cellular morphology, migration, adhesion, and other various biological functions [36, 37]. Various cytokines and inflammatory factors can activate the Rho/Rho kinase pathway, causing myosin light-chain phosphorylation, actin-myosin cross-linking enhancement, F-actin cytoskeleton recombination, and stress fibre formation [38].…”