Tight Junctions in the Auditory System: Structure, Distribution and Function

Abstract

Tight junctions act as a barrier between epithelial cells to limit the transport of the paracellular substance, which is a required function in various tissues to sequestrate diverse microenvironments and maintain a normal physiological state. Tight junctions are complexes that contain various proteins, like transmembrane proteins, scaffolding proteins, signaling proteins, etc. Defects in those tight junction-related proteins can lead to hearing loss in humans which is also recapitulated in many model organisms. The disruption of the barrier between the endolymph and perilymph caused by tight junction abnormalities will affect the microenvironment of hair cells; and this could be the reason for this type of hearing loss. Besides their functions as a typical barrier and channel, tight junctions are also involved in many signaling networks to regulate gene expression, cell proliferation, and differentiation. This review will summarize the structures, localization, and related signaling pathways of hearing-related tight junction proteins and their potential contributions to the hearing disorder.

Cingulin regulates hair cell cuticular plate morphology and is required for hearing in human and mouse

“…Tight junctions (TJs) are specialized intercellular junctions that form a continuous, belt‐like seal between adjacent cells in epithelial and endothelial tissues (Sawada et al , 2003 ). TJs in the inner ear are critical for the maintenance of the unique fluid environment in the cochlea and of the electrochemical gradient that drives mechanotransduction of sound (Gao et al , 2023 ). Defects in multiple tight junction‐related proteins, such as ZO‐2 ( TJP2 ), claudin‐9 ( CLDN9 ), claudin‐14 ( CLDN14 ), and claudin‐11 ( CLDN11 ) are associated with hearing loss in humans and mice (Wilcox et al , 2001 ; Gow et al , 2004 ; Walsh et al , 2010 ; Sineni et al , 2019 ).…”