A new compartment at stereocilia tips defined by spatial and temporal patterns of myosin IIIa expression.
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.
Schneider
Mark E
ME
Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
Dosé
Andréa C
AC
Salles
Felipe T
FT
Chang
Weise
W
Erickson
Floyd L
FL
Burnside
Beth
B
Kachar
Bechara
B
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
C491724:MYO3A protein, human; D025102:Myosin Type III; D018995:Myosin Heavy Chains