Radixin, often referred to as Rdx, is a critical protein belonging to the Ezrin, Radixin, Moesin (ERM) family. These proteins are fundamental in crosslinking actin filaments with integral membrane proteins, playing essential roles in cell structure and function. Research leveraging mouse models has brought to light the significant functions of Radixin, particularly in liver physiology and auditory mechanisms. This article will explore these crucial roles based on key scientific investigations.
Radixin’s involvement in liver function is primarily centered on the secretion of conjugated bilirubin. Studies indicate that Radixin is the predominant ERM protein found in the liver of wildtype mice, with a high concentration at bile canalicular membranes (BCM). Research into Radixin-deficient (Rdx -/-) mice has revealed a direct link between its absence and the development of conjugated hyperbilirubinemia. This condition mirrors human conjugated hyperbilirubinemia seen in Dubin-Johnson syndrome, although the latter is not typically associated with liver injury. The investigation further pinpointed Radixin’s crucial role in the localization of multidrug resistance protein-2 (MRP2) at BCMs. MRP2 is vital for transporting conjugated bilirubin into bile for excretion. In Rdx -/- mice, a significant reduction of Mrp2 was observed in BCMs compared to other BCM proteins, such as dipeptidyl peptidase IV. This deficiency directly impairs the secretion of conjugated bilirubin. In vitro binding assays have confirmed that radixin directly interacts with the C-terminal cytoplasmic domain of human MRP2, reinforcing its essential support role in MRP2 localization and function at BCMs.
Beyond its hepatic functions, Radixin is also indispensable for auditory function. It is notably enriched in the stereocilia of cochlear hair cells, which are critical sensory structures for hearing. Studies on Rdx-null adult mice have demonstrated that these mice suffer from deafness due to the progressive degeneration of cochlear stereocilia. Interestingly, vestibular stereocilia, similar structures responsible for balance, remain unaffected in Radixin-deficient mice. This suggests a compensatory mechanism, possibly involving ezrin, another ERM protein, in vestibular stereocilia. These findings underscore that Radixin is specifically and critically required for the maintenance of cochlear stereocilia integrity, and consequently, for hearing ability in mice.
In conclusion, Radixin (Rdx) emerges as a pivotal ERM protein with dual critical roles in maintaining liver function and hearing. Research utilizing mouse models has clearly demonstrated its necessity for effective bilirubin secretion through MRP2 in the liver and for the structural stability of cochlear stereocilia in the auditory system. These insights highlight the diverse and vital physiological functions of Radixin within mammalian systems.
