Effect of oncomodulin on cytoskeletal actin dynamics.
Cochlear outer hair cells (OHCs) contribute to the fine sensitivity of the mammalian auditory system by serving as a feedback mechanism in response to sound. Regulation of filamentous and globular actin may contribute to the reversible shape changes critical to OHC function. Previous studies have suggested that the Rho family of GTPases play an important role in regulating intracellular actin dynamics in OHCs using RhoA/ROCK and LIMK/cofilin mediated pathways. We hypothesize that modulation of calcium signaling through mobile calcium buffers alters intracellular actin dynamics in OHCs. Early studies of OHC lateral stiffness and motility suggest that calcium modifies the actin-based cortical cytoskeleton. An EF-hand calcium buffering protein, oncomodulin (OCM) is preferentially expressed in OHCs and may aid in sculpting calcium signals important for actin remodeling. Targeted deletion of OCM leads to early progressive hearing loss in mice without severe OHC loss suggesting the importance of OCM to OHC function.
Networked Digital Library of Theses and Dissertations