title: Myosin light-chain kinase is necessary for membrane homeostasis in cochlear inner hair cells.
abstract: The structural homeostasis of the cochlear hair cell membrane is critical for all aspects of sensory transduction, but the regulation of its maintenance is not well understood. In this report, we analyzed the cochlear hair cells of mice with specific deletion of myosin light chain kinase (MLCK) in inner hair cells. MLCK-deficient mice showed impaired hearing, with a 5- to 14-dB rise in the auditory brainstem response (ABR) thresholds to clicks and tones of different frequencies and a significant decrease in the amplitude of the ABR waves. The mutant inner hair cells produced several ball-like structures around the hair bundles in vivo, indicating impaired membrane stability. Inner hair cells isolated from the knockout mice consistently displayed less resistance to hypoosmotic solution and less membrane F-actin. Myosin light-chain phosphorylation was also reduced in the mutated inner hair cells. Our results suggest that MLCK is necessary for maintaining the membrane stability of inner hair cells.
authors.affiliation: MOE Key Laboratory for Model Animal and Diseases Studies, Nanjing Drum Tower Hospital and Model Animal Research Center of Nanjing University, Nanjing, China.
authors.forename: Guang-Jie
authors.initials: GJ
authors.lastname: Zhu
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Zhang
authors.forename: Chi
authors.initials: C
authors.lastname: Fan
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Peng
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Wei-Qi
authors.initials: WQ
authors.lastname: He
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Guo
authors.forename: Jian
authors.initials: J
authors.lastname: Zuo
authors.forename: Xia
authors.initials: X
authors.lastname: Gao
authors.forename: Min-Sheng
authors.initials: MS
authors.lastname: Zhu
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology* / Q000378:metabolism; D004848:Epithelium / Q000201:enzymology / Q000378:metabolism; D016057:Evoked Potentials, Auditory, Brain Stem; D015870:Gene Expression; D006199:Hair Cells, Auditory, Inner / Q000201:enzymology* / Q000378:metabolism / Q000648:ultrastructure; D006706:Homeostasis; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018994:Myosin Light Chains / Q000378:metabolism; D000081412:Myosin VIIa; D009219:Myosin-Light-Chain Kinase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009218:Myosins / Q000378:metabolism; D009925:Organ of Corti / Q000166:cytology; D009997:Osmotic Pressure; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017384:Sequence Deletion; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; C521958:Mylpf protein, mouse; C000631456:Myo7a protein, mouse; D018994:Myosin Light Chains; D000081412:Myosin VIIa; D009219:Myosin-Light-Chain Kinase; D009218:Myosins; D000254:Sodium-Potassium-Exchanging ATPase