Gamma-Actin's Influence on Cell Rigidity and Junctional Proteins

Epithelial cells defend human skin and mucous membranes. Specialized structures known as “junctions” enable this “barrier” tissue to carry out its role. They control interactions between cells and maintain cell cohesion.

In cooperation with the National University of Singapore (NUS) and the Institute of Physical Chemistry (IPC) in Göttingen, researchers at the University of Geneva (UNIGE) have investigated the function of a particular protein, gamma-actin, in the structure and dynamics of epithelial cells and their junctions.

A system of interdependence between various versions of the cytoskeletal proteins actin and myosin and their roles is revealed by their work, which was published in Nature Communications. The group also shows how gamma-actin plays a crucial part in junctional protein dynamics and cell membrane stiffness, which could explain hearing loss.

The epithelium, which lines the inside of several organs and covers the body's surface, is a tissue of vital importance. It is made up of closely packed epithelial cells and is essential for defense against infections and other external threats.

The presence of “adherens” and “tight junctions,” which are essentially protein locks connecting nearby cells and guaranteeing tissue tightness, is crucial to this function. The flow of molecules into and out of organs is controlled by tight junctions. For instance, they aid in the kidneys' filtration of chemicals and the intestinal absorption of nutrients.

Sandra Citi is an Associate Professor in the Department of Molecular and Cellular Biology at the UNIGE Faculty of Science. Her lab focuses on the different roles that the epithelium plays and how tight junctions interact with the cytoskeleton, which is the internal framework of cells, to control cell architecture.

A Possible Cause Of Deafness?

In a recent study, the researcher and her team examined how gamma-actin, a cytoskeleton component, organizes cell-to-cell junctions. They found that when gamma-actin is absent, beta-actin, another form of actin, is produced in higher amounts, which is associated with an increase in a particular type 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.”

Marine Maupérin, Postdoctoral Fellow and Study First Author, Department of Molecular and Cellular Biology, University of Geneva

As a result, gamma-actin gives the apical membrane more stiffness, creating a stronger and stiffer filament network than that composed of beta-actin filaments.

“This result is particularly interesting because the stiffness of the apical membrane is essential for auditory function,” explained Sandra Citi, who led this research.

Animals lacking gamma-actin exhibit gradual hearing loss and changed apical surface epithelial cell morphology. The hair cells lining the inner ear are subjected to continuous mechanical stimulation, which may necessitate a stronger cortical membrane.

Thus, a more thorough examination of gamma-actin's function in preserving cell integrity may aid in the understanding of diseases like hearing loss.