Cochlear hair cells are extremely sensitive to stress and loss of these cells is a common cause of deafness. Within the inner ear, there are 2 compositionally distinct fluids, the endolymph and the perilymph, which are compartmentalized by the epithelial cells lining the cochlea. Formation of tight junctions between epithelial cells prevents the free exchange of fluid and other molecules. Gowri Nayak and colleagues at the Cincinnati Children’s Hospital, identify a role for the tricellular tight junction protein, TRIC, in cochlear hair cell preservation. A mutation in the TRIC gene had been previously linked to hearing loss in humans; however, the mechanism of hearing loss was unknown. The authors generated a transgenic mouse model harboring the human hearing loss-associated TRIC mutation. These mice progressively lost both cochlear hair cells and hearing. The authors found that the tight junctions between cochlear epithelial cells in these mice were altered and lacked TRIC. Their data suggests that mutated TRIC creates a toxic environment in the cochlea due to free exchange between the endolymph and the perilymph due to fewer tight cell junctions. In the accompanying commentary, Karen Avraham and colleagues from Tel Aviv University point out that this new mouse model will provide insights into human TRIC-associated deafness and how tight junction function can be restored. On the left is an electron microscopy image of a freeze fracture replica showing the tricellular tight junction of an Outer Hair Cell in the mouse organ of Corti. The image on the right is a 3D reconstruction collage of confocal images of marginal cells from mouse stria vascularis stained with anti-tricellulin antibody (red) and an antibody specific to tight-junction associated protein ZO1 (green).
The two compositionally distinct extracellular cochlear fluids, endolymph and perilymph, are separated by tight junctions that outline the scala media and reticular lamina. Mutations in
Gowri Nayak, Sue I. Lee, Rizwan Yousaf, Stephanie E. Edelmann, Claire Trincot, Christina M. Van Itallie, Ghanshyam P. Sinha, Maria Rafeeq, Sherri M. Jones, Inna A. Belyantseva, James M. Anderson, Andrew Forge, Gregory I. Frolenkov, Saima Riazuddin
Tricellulin is a tricellular tight junction–associated membrane protein that controls movement of solutes at these specialized cell intersections. Mutations in the gene encoding tricellulin,
Tomohito Higashi, Danielle R. Lenz, Mikio Furuse, Karen B. Avraham