title: A new compartment at stereocilia tips defined by spatial and temporal patterns of myosin IIIa expression.
abstract: Class III myosins are motor proteins that contain an N-terminal kinase domain and a C-terminal actin-binding domain. We show that myosin IIIa, which has been implicated in nonsyndromic progressive hearing loss, is localized at stereocilia tips. Myosin IIIa progressively accumulates during stereocilia maturation in a thimble-like pattern around the stereocilia tip, distinct from the cap-like localization of myosin XVa and the shaft localization of myosin Ic. Overexpression of deletion mutants for functional domains of green fluorescent protein (GFP)-myosin IIIa shows that the motor domain, but not the actin-binding tail domain, is required for stereocilia tip localization. Deletion of the kinase domain produces stereocilia elongation and bulging of the stereocilia tips. The thimble-like localization and the influence myosin IIIa has on stereocilia shape reveal a previously unrecognized molecular compartment at the distal end of stereocilia, the site of actin polymerization as well as operation of the mechanoelectrical transduction apparatus.
authors.affiliation: Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Schneider
authors.forename: Andréa C
authors.initials: AC
authors.lastname: Dosé
authors.forename: Felipe T
authors.initials: FT
authors.lastname: Salles
authors.forename: Weise
authors.initials: W
authors.lastname: Chang
authors.forename: Floyd L
authors.initials: FL
authors.lastname: Erickson
authors.forename: Beth
authors.initials: B
authors.lastname: Burnside
authors.forename: Bechara
authors.initials: B
authors.lastname: Kachar
mesh_terms: D000818:Animals; D001001:Anura; D001492:Bass; D019556:COS Cells; D002478:Cells, Cultured; D002645:Chickens; D002522:Chlorocebus aethiops; D002923:Cilia / Q000235:genetics / Q000378:metabolism; D007758:Ear, Inner / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D018995:Myosin Heavy Chains / Q000096:biosynthesis* / Q000235:genetics; D025102:Myosin Type III / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D013997:Time Factors
chemical_list: C491724:MYO3A protein, human; D025102:Myosin Type III; D018995:Myosin Heavy Chains