Our body is composed of approximately 30 trillion cells, each of which must tightly adhere to its neighbors to preserve the overall integrity of our physical form. However, we are constantly subjected to mechanical stresses, whether from daily activities or unexpected events like falls. How do our cells resist these forces to prevent our body from falling apart? The secret lies in the intricate cell-to-cell adhesion apparatus, which includes three primary types of junctions: tight junctions, adherens junctions, and desmosomes. Previous research has highlighted the critical roles of adherens junctions and desmosomes in maintaining bodily integrity, but the specific contributions of tight junctions have remained elusive.
One of the key challenges in understanding the function of tight junctions was the difficulty in selectively and completely eliminating their activity, due to the overlapping roles of their key components. A few years ago, a team led by researchers at the National Institute for Physiological Sciences in Japan, succeeded in generating an epithelial cell line that lacked the tight junction membrane proteins claudins and JAM-A, effectively eliminating tight junctions. Upon closer examination of these cells, the researchers made a surprising discovery: while normal cells maintain a continuous belt of cell-to-cell junctions, the cells lacking tight junctions exhibited sporadic disruption and fragmentation of these connections. Intrigued by this observation, the researchers decided to investigate further.
By capturing time-lapse videos, the team found that the cell-to-cell junctions in the tight junction-deficient cells fractured when the cells were stretched. This led them to the conclusion that tight junction membrane proteins play a crucial role in regulating the conformation of a protein called ZO-1, which acts as a mechanosensor to help cells resist mechanical stress.
According to Mikio Furuse, senior author of the study published in the Journal of Cell Biology, “This study shows that tight junctions in addition to adherens junctions and desmosomes are important for cells to resist mechanical stress. An interesting question is why we need so many junctions to resist force, and how these junctions collaborate to provide mechanical resistance. We would like to tackle these issues in the future.”