title: Activity-dependent regulation of prestin expression in mouse outer hair cells.
abstract: Prestin is a membrane protein necessary for outer hair cell (OHC) electromotility and normal hearing. Its regulatory mechanisms are unknown. Several mouse models of hearing loss demonstrate increased prestin, inspiring us to investigate how hearing loss might feedback onto OHCs. To test whether centrally mediated feedback regulates prestin, we developed a novel model of inner hair cell loss. Injection of diphtheria toxin (DT) into adult CBA mice produced significant loss of inner hair cells without affecting OHCs. Thus, DT-injected mice were deaf because they had no afferent auditory input despite OHCs continuing to receive normal auditory mechanical stimulation and having normal function. Patch-clamp experiments demonstrated no change in OHC prestin, indicating that loss of information transfer centrally did not alter prestin expression. To test whether local mechanical feedback regulates prestin, we used Tecta(C1509G) mice, where the tectorial membrane is malformed and only some OHCs are stimulated. OHCs connected to the tectorial membrane had normal prestin levels, whereas OHCs not connected to the tectorial membrane had elevated prestin levels, supporting an activity-dependent model. To test whether the endocochlear potential was necessary for prestin regulation, we studied Tecta(C1509G) mice at different developmental ages. OHCs not connected to the tectorial membrane had lower than normal prestin levels before the onset of the endocochlear potential and higher than normal prestin levels after the onset of the endocochlear potential. Taken together, these data indicate that OHC prestin levels are regulated through local feedback that requires mechanoelectrical transduction currents. This adaptation may serve to compensate for variations in the local mechanical environment.
authors: Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California.
authors: Yohan
authors: Y
authors: Song
authors: Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California.
authors: Anping
authors: A
authors: Xia
authors: Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California.
authors: Hee Yoon
authors: HY
authors: Lee
authors: Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California.
authors: Rosalie
authors: R
authors: Wang
authors: Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California.
authors: Anthony J
authors: AJ
authors: Ricci
authors: Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California joghalai@stanford.edu.
authors: John S
authors: JS
authors: Oghalai
mesh_terms: D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000187:drug effects; D004167:Diphtheria Toxin / Q000494:pharmacology; D025802:Electric Capacitance; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D058851:GPI-Linked Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic / Q000235:genetics; D008855:Microscopy, Electron, Scanning; D020409:Molecular Motor Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D017084:Otoacoustic Emissions, Spontaneous / Q000235:genetics; D018408:Patch-Clamp Techniques
chemical_list: D004167:Diphtheria Toxin; D016326:Extracellular Matrix Proteins; D058851:GPI-Linked Proteins; D020409:Molecular Motor Proteins; C498720:Pres protein, mouse; C105350:Tecta protein, mouse
keywords: cochlea; electromotility; hair cell; hearing; mechanics; prestin