ArticleJournal of neurochemistry2015
Noise-induced cochlear F-actin depolymerization is mediated via ROCK2/p-ERM signaling.
Article in Journal of neurochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- OSBPL2 deficiency inhibits Rho/ROCK2/p-ERM signaling and impairs actin cytoskeletal regulation in auditory cells.Journal of biomedical research · 2025Article
- Lysophosphatidic acid exerts protective effects on HEI-OC1 cells against cytotoxicity of cisplatin by decreasing apoptosis, excessive autophagy, and accumulation of ROS.Cell death discovery · 2023Article
- The role of Rho GTPase family in cochlear hair cells and hearing.Neural regeneration research · 2023Review
- Prevention of noise-induced hearing loss by calpain inhibitor MDL-28170 is associated with upregulation of PI3K/Akt survival signaling pathway.Frontiers in cellular neuroscience · 2023Article
- Downregulation of GJB2 and SLC26A4 genes induced by noise exposure is associated with cochlear damage.Molecular biology reports · 2022Article
- Collapsin Response Mediator Protein 1 (CRMP1) Is Required for High-Frequency Hearing.The American journal of pathology · 2022Article
- Lysophosphatidic Acid Induced Apoptosis, DNA Damage, and Oxidative Stress in Spinal Cord Neurons by Upregulating LPA4/LPA6 Receptors.Mediators of inflammation · 2022Article
- Primed to die: an investigation of the genetic mechanisms underlying noise-induced hearing loss and cochlear damage in homozygous Foxo3-knockout mice.Cell death & disease · 2021Article
- Seagrass Posidonia is impaired by human-generated noise.Communications biology · 2021Article
- Matrix Metalloproteinase-9 Overexpression Regulates Hippocampal Synaptic Plasticity and Decreases Alcohol Consumption and Preference in Mice.Neurochemical research · 2020Article
- The integrity of cochlear hair cells is established and maintained through the localization of Dia1 at apical junctional complexes and stereocilia.Cell death & disease · 2020Article
- The receptor tyrosine kinase EPHB6 regulates catecholamine exocytosis in adrenal gland chromaffin cells.The Journal of biological chemistry · 2020Article
- Quantitative in situ proximity ligation assays examining protein interactions and phosphorylation during smooth muscle contractions.Analytical biochemistry · 2019Article
- Inhibition of Histone Methyltransferase G9a Attenuates Noise-Induced Cochlear Synaptopathy and Hearing Loss.Journal of the Association for Research in Otolaryngology : JARO · 2019Article
- Otoprotective Effects of Stephania tetrandra S. Moore Herb Isolate against Acoustic Trauma.Journal of the Association for Research in Otolaryngology : JARO · 2018Article
- Inactivation of Cyclin-Dependent Kinase 5 in Hair Cells Causes Hearing Loss in Mice.Frontiers in molecular neuroscience · 2018Article
- Actin polymerization is reduced in the anterior cingulate cortex of elderly patients with schizophrenia.Translational psychiatry · 2017Article
- The BEACH protein LRBA is required for hair bundle maintenance in cochlear hair cells and for hearing.EMBO reports · 2017Article
- Conditional deletion of pejvakin in adult outer hair cells causes progressive hearing loss in mice.Neuroscience · 2017Article
- The role of post-translational modifications in hearing and deafness.Cellular and molecular life sciences : CMLS · 2016Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Our previous work has suggested that traumatic noise activates Rho-GTPase pathways in cochlear outer hair cells (OHCs), resulting in cell death and noise-induced hearing loss (NIHL). In this study, we investigated Rho effectors, Rho-associated kinases (ROCKs), and the targets of ROCKs, the ezrin-radixin-moesin (ERM) proteins, in the regulation of the cochlear actin cytoskeleton using adult CBA/J mice under conditions of noise-induced temporary threshold shift (TTS) and permanent threshold shift (PTS) hearing loss, which result in changes to the F/G-actin ratio. The levels of cochlear ROCK2 and p-ERM decreased 1 h after either TTS- or PTS-noise exposure. In contrast, ROCK2 and p-ERM in OHCs decreased only after PTS-, not after TTS-noise exposure. Treatment with lysophosphatidic acid, an activator of the Rho pathway, resulted in significant reversal of the F/G-actin ratio changes caused by noise exposure and attenuated OHC death and NIHL. Conversely, the down-regulation of ROCK2 by pretreatment with ROCK2 siRNA reduced the expression of ROCK2 and p-ERM in OHCs, exacerbated TTS to PTS, and worsened OHC loss. Additionally, pretreatment with siRNA against radixin, an ERM protein, aggravated TTS to PTS. Our results indicate that a ROCK2-mediated ERM-phosphorylation signaling cascade modulates noise-induced hair cell loss and NIHL by targeting the cytoskeleton. We propose the following cascade following noise trauma leading to alteration of the F-actin arrangement in the outer hair cell cytoskeleton: Noise exposure reduces the levels of GTP-RhoA and subsequently diminishes levels of RhoA effector ROCK2 (Rho-associated kinase 2). Phosphorylation of ezrin-radixin-moesin (ERM) by ROCK2 normally allows ERM to cross-link actin filaments with the plasma membrane. Noise-decreased levels of ROCK results in reduction of phosphorylation of ERM that leads to depolymerization of actin filaments. Lysophosphatidic acid (LPA), an agonist of RhoA, binds to the G-protein-coupled receptor (GPCR) leading to activation of RhoA through Gα12/13 and RhoGEF. Administration of LPA rescues the noise-diminished F/G-actin ratio.
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