Our skin and mucous membranes protect us like vigilant sentinels against the onslaught of harmful pathogens. This extraordinary defense owes its strength to epithelial cells—specialized tissues woven together by microscopic “junctions,” which function as gatekeepers for cell cohesion and molecular exchanges.
A groundbreaking study led by 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, has unveiled a surprising new twist in how epithelial cells maintain their structure and function.
The findings cast light on a key protein—gamma-actin—and its essential role in protecting the integrity of these cellular barriers. The revelation carries profound implications, including a potential explanation for certain forms of hearing loss.
The epithelium, a tissue of remarkable precision, serves as both armor and filter for our bodies. Whether warding off external aggressors or carefully regulating the passage of nutrients and toxins in vital organs like the intestines and kidneys, the epithelium is a masterpiece of cellular design. Its impenetrable nature is bolstered by two molecular locks—adherents and tight junctions—that bind epithelial cells together.
Sandra Citi, Associate Professor in the Department of Molecular and Cellular Biology at UNIGE, has long been fascinated by these tiny locks and their interaction with the cytoskeleton, a cell’s internal framework.
This new study by her team focused on gamma-actin, a lesser-known protein. It revealed a complex interplay between different forms of cytoskeletal proteins—gamma-actin, beta-actin, and their partner, myosin.
The researchers discovered that the absence of gamma-actin triggers an unexpected reaction. Cells ramp up production of beta-actin, accompanied by a specific form of myosin. While this adaptation keeps the tight junctions functioning, it comes with a hidden cost: the apical membrane—the cell’s upper surface—becomes less rigid.
“Gamma-actin forms a stronger, stiffer network of filaments than beta-actin,” explains Marine Maupérin, the study’s first author. “This rigidity is crucial for maintaining the epithelium’s architecture and functions like auditory signaling.”
The implications of gamma-actin’s absence are particularly striking in auditory health. Mice deficient in gamma-actin exhibit structural changes in the apical surface of epithelial cells and progressive hearing loss. The researchers propose that a stiffer cortical membrane is vital for the sensory hair cells in the inner ear, which endure relentless mechanical stress from sound waves.
This revelation opens a new frontier in understanding hearing loss. “The interplay of actin forms and their impact on cell mechanics provides a deeper insight into how epithelial tissues maintain their integrity under stress,” says Sandra Citi. “It also hints at a potential molecular target for therapies to preserve hearing.”
The study sheds light on the intricate balance of proteins within our cells and underscores the resilience of epithelial tissues. Even when the delicate equilibrium is disrupted, cells find ways to adapt—albeit at a cost.
For now, the discovery of gamma-actin’s pivotal role reminds us of the unseen marvels that keep our bodies functioning. From shielding us against pathogens to enabling the miracle of hearing, our cells are engaged in a never-ending dance of cooperation and adaptation. This research takes us one step closer to decoding the choreography.
Journal Reference:
- Maupérin, M., Sun, Y., Glandorf, T. et al. A feedback circuitry involving γ-actin, β-actin and nonmuscle myosin-2 A controls tight junction and apical cortex mechanics. Nat Commun 16, 2514 (2025). DOI: 10.1038/s41467-025-57428-y
Source: Tech Explorist
