Journal
NEURAL REGENERATION RESEARCH
Volume 18, Issue 10, Pages 2167-2172Publisher
WOLTERS KLUWER MEDKNOW PUBLICATIONS
DOI: 10.4103/1673-5374.369101
Keywords
actin assembly; auditory sensory neurons; cell polarity; cell proliferation; electromotility; hair cell; hearing loss; morphogenesis; Rho GTPases; stereocilia
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Rho GTPases are crucial regulators of the actin cytoskeleton, involved in various physiological and biochemical processes. RhoA, Cdc42, and Rac1, members of the classical subfamily of Rho GTPases, play a role in the development and maintenance of cilia in cochlear hair cells. They also regulate the orientation of ciliary bundles and contribute to the motility of outer hair cells in the auditory sensory system. This review focuses on the expression of RhoA, Cdc42, and Rac1 in cochlear hair cells and their involvement in ciliary bundle morphogenesis and hair cell movement, as well as their potential as drug targets for deafness treatment.
Rho GTPases are essential regulators of the actin cytoskeleton. They are involved in various physiological and biochemical processes such as the regulation of cytoskeleton dynamics, development, proliferation, survival, and regeneration. During the development of cochlear hair cells, Rho GTPases are activated by various extracellular signals through membrane receptors to further stimulate multiple downstream effectors. Specifically, RhoA, Cdc42, and Rac1, members of the classical subfamily of the Rho GTPase family, regulate the development and maintenance of cilia by inducing the polymerization of actin monomers and stabilizing actin filaments. In addition, they also regulate the normal morphology orientation of ciliary bundles in auditory hair cells, which is an important element of cell polarity regulation. Moreover, the actin-related pathways mediated by RhoA, Cdc42, and Rac1 also play a role in the motility of outer hair cells, indicating that the function of Rho GTPases is crucial in the highly polar auditory sensory system. In this review, we focus on the expression of RhoA, Cdc42, and Rac1 in cochlear hair cells and how these small molecules participate in ciliary bundle morphogenesis and cochlear hair cell movement. We also discuss the progress of current research investigating the use of these small molecules as drug targets for deafness treatment.
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