Myosin light chain kinase regulates hearing in mice by influencing the F-actin cytoskeleton of outer hair cells and cochleae.
Myosin light chain kinase (MLCK) phosphorylates myosin regulatory light chains to facilitate its interaction with actin filaments and produce contractile activity. The outer hair cells (OHCs) in the ear contain large amounts of actin and a variety myosins. The stereociliary and somatic motility of OHCs are closely related to hearing. It appears likely that MLCK may play an important role in acoustic trans-duction. In this study, we analyzed, both in vivo and in vitro, the OHCs of mice bearing a specific deletion of the MLCK gene and the OHCs of control mice. The phenotype was assessed by auditory function [acoustic brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs)], inner ear morphology and histology. MLCK-deficient mice aged 6-7 months showed impaired hearing, a 5- to 10-dB sound pressure level (SPL) increase in the ABR thresholds, when responding to clicks and tones of different frequencies (8 and 16 kHz) (P<0.05). The DPOAE amplitudes of 3-month-old MLCK-deficient mice decreased significantly (>10 dB SPL) at low frequencies (4, 5 and 6 kHz). The OHCs in the MLCK-deficient mice increased with abnormal stereocilia. The staining of F-actin and the phosphorylation of the regulatory light chain in MLCK-deficient OHCs was weak. Our results indicate that MLCK may regulate the structure and the motility of stereocilia through F-actin polymerization.
Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing 210008, P.R. China.
Xia
X
Yang
Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing 210008, P.R. China.
Jun-Guo
JG
Wang
Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing 210008, P.R. China.
Deng-Bin
DB
Ma
Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing 210008, P.R. China.
Xiao-Feng
XF
Ma
Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing 210008, P.R. China.
Guang-Jie
GJ
Zhu
Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing 210008, P.R. China.
Han
H
Zhou
Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing 210008, P.R. China.
Chen-Jie
CJ
Yu
Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing 210008, P.R. China.
Xiao-Yun
XY
Qian
Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing 210008, P.R. China.
Xia
X
Gao
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001309:Auditory Threshold / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005455:Fluorescent Antibody Technique; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000201:enzymology* / Q000502:physiology* / Q000648:ultrastructure; D006309:Hearing / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018994:Myosin Light Chains / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000172:deficiency / Q000378:metabolism*; D017084:Otoacoustic Emissions, Spontaneous / Q000502:physiology; D010766:Phosphorylation
D000199:Actins; D018994:Myosin Light Chains; D009219:Myosin-Light-Chain Kinase