Our skin and mucous membranes are protected by epithelial cells, which form a barrier that defends the body from the outside environment. This barrier function relies on specialized structures called junctions that hold cells together and regulate the exchange of substances between them.
Researchers at the University of Geneva (UNIGE), in collaboration with the National University of Singapore (NUS) and the Institute of Physical Chemistry (IPC) in Göttingen, investigated the role of a specific protein called gamma-actin in shaping the structure and mechanical properties of epithelial cells and their junctions. Their findings, published in Nature Communications, uncover a mechanism of interdependence between different forms of the cytoskeletal proteins actin and myosin. The study also highlights gamma-actin’s critical role in maintaining cell membrane stiffness and controlling the movement of junctional proteins – factors that may help explain certain forms of hearing loss.
Essential Role of Epithelium
The epithelium is a tissue of fundamental importance, that covers the surface of the body and lines the interior of many organs. Composed of tightly bound epithelial cells, it plays a crucial protective role against external aggressions, such as pathogens. This function relies to a large extent on the presence of “adherens” and “tight junctions,” veritable protein locks linking neighboring cells and ensuring tissue tightness. Tight junctions regulate the passage of molecules in and out of organs. For example, they facilitate nutrient absorption in the intestine and help filter substances in the kidneys.
The laboratory of Sandra Citi, Associate Professor in the Department of Molecular and Cellular Biology at the UNIGE Faculty of Science, is interested in how tight junctions interact with the cytoskeleton – the internal framework of cells – to regulate cell architecture, as well as the various functions performed by the epithelium.
Exploring Gamma-Actin’s Impact on Hearing
In this recent study, the researcher and her team analyzed the role of gamma-actin – one of the components of the cytoskeleton – in the organization of junctions between cells, and discovered that in its absence another form of actin, beta-actin, is produced in greater quantities, and this is linked to an increase in a specific form of myosin. “These changes make the apical membrane – the top of the cell – less stiff and certain constituents of the tight junctions more mobile, without however affecting the barrier formed by these junctions,” explains Marine Maupérin, postdoctoral fellow in the Department of Molecular and Cellular Biology at the UNIGE Faculty of Science and first author of the study.
Key Insights into Gamma-Actin and Hearing Loss
Gamma-actin therefore confers increased rigidity to the apical membrane, forming a network of filaments that is stronger and stiffer than that made up of beta-actin filaments. “This result is particularly interesting because the stiffness of the apical membrane is essential for auditory function,” explains Sandra Citi, who led this research.
Indeed, gamma-actin-deficient mice show altered architecture of the apical surface of epithelial cells and progressive hearing loss. A stiffer cortical membrane may be required to withstand the constant mechanical stimuli to which the hair cells lining the inner ear are exposed. A deeper investigation into the role of gamma-actin in maintaining cell integrity could thus help to understand the pathologies of hearing loss, for example.
Reference: “A feedback circuitry involving γ-actin, β-actin and nonmuscle myosin-2 A controls tight junction and apical cortex mechanics” by Marine Maupérin, Yuze Sun, Thomas Glandorf, Tabea Anne Oswald, Niklas Klatt, Burkhard Geil, Annick Mutero-Maeda, Isabelle Méan, Lionel Jond, Andreas Janshoff, Jie Yan and Sandra Citi, 13 March 2025, Nature Communications.
DOI: 10.1038/s41467-025-57428-y
