title: Balanced levels of Espin are critical for stereociliary growth and length maintenance.
abstract: Hearing and balance depend on microvilli-like actin-based projections of sensory hair cells called stereocilia. Their sensitivity to mechanical displacements on the nanometer scale requires a highly organized hair bundle in which the physical dimension of each stereocilium is tightly controlled. The length and diameter of each stereocilium are established during hair bundle maturation and maintained by life-long continuing dynamic regulation. Here, we studied the role of the actin-bundling protein Espin in stereociliary growth by examining the hair cell stereocilia of Espin-deficient jerker mice (Espn(je)), and the effects of transiently overexpressing Espin in the neuroepithelial cells of the organ of Corti cultures. Using fluorescence scanning confocal and electron microscopy, we found that a lack of Espin results in inhibition of stereociliary growth followed by progressive degeneration of the hair bundle. In contrast, overexpression of Espin induced lengthening of stereocilia and microvilli that mirrored the elongation of the actin filament bundle at their core. Interestingly, Espin deficiency also appeared to influence the localization of Myosin XVa, an unconventional myosin that is normally present at the stereocilia tip at levels proportional to stereocilia length. These results indicate that Espin is important for the growth and maintenance of the actin-based protrusions of inner ear neuroepithelial cells.
authors.affiliation: Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892-8027, USA.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Rzadzinska
authors.forename: Mark
authors.initials: M
authors.lastname: Schneider
authors.forename: Konrad
authors.initials: K
authors.lastname: Noben-Trauth
authors.forename: James R
authors.initials: JR
authors.lastname: Bartles
authors.forename: Bechara
authors.initials: B
authors.lastname: Kachar
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002923:Cilia / Q000378:metabolism / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D006199:Hair Cells, Auditory, Inner / Q000254:growth & development* / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D018613:Microscopy, Confocal; D008871:Microvilli / Q000378:metabolism / Q000648:ultrastructure; D009218:Myosins / Q000378:metabolism; D009925:Organ of Corti / Q000254:growth & development / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014722:Vestibule, Labyrinth / Q000254:growth & development / Q000378:metabolism
chemical_list: D008840:Microfilament Proteins; C114013:Myo15 protein, mouse; D011993:Recombinant Fusion Proteins; C104108:espin protein, mouse; D049452:Green Fluorescent Proteins; D009218:Myosins