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The Journal of Neuroscience, October 4, 2006, 26(40):10243-10252; doi:10.1523/JNEUROSCI.2812-06.2006

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Cellular/Molecular
A New Compartment at Stereocilia Tips Defined by Spatial and Temporal Patterns of Myosin IIIa Expression

Mark E. Schneider,^1 * Andréa C. Dosé,^2 * Felipe T. Salles,^1 * Weise Chang,¹ Floyd L. Erickson,³ Beth Burnside,² and Bechara Kachar¹

¹Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, ²Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, and ³Department of Biological Sciences, Salisbury University, Salisbury, Maryland 21801

Correspondence should be addressed to Dr. Bechara Kachar, Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Building 50, Room 4249, 50 South Drive, Bethesda, MD 20892-8027. Email: kacharb{at}nidcd.nih.gov

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.

Key words: hair cells; myosin IIIa; stereocilia; hearing; myosin XVa; myosin Ic

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Received July 1, 2006; revised Aug. 7, 2006; accepted Aug. 17, 2006.

Correspondence should be addressed to Dr. Bechara Kachar, Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Building 50, Room 4249, 50 South Drive, Bethesda, MD 20892-8027. Email: kacharb{at}nidcd.nih.gov

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				G. Lefevre, V. Michel, D. Weil, L. Lepelletier, E. Bizard, U. Wolfrum, J.-P. Hardelin, and C. Petit A core cochlear phenotype in USH1 mouse mutants implicates fibrous links of the hair bundle in its cohesion, orientation and differential growth Development, April 15, 2008; 135(8): 1427 - 1437. [Abstract] [Full Text] [PDF]

				J. Waguespack, F. T. Salles, B. Kachar, and A. J. Ricci Stepwise Morphological and Functional Maturation of Mechanotransduction in Rat Outer Hair Cells J. Neurosci., December 12, 2007; 27(50): 13890 - 13902. [Abstract] [Full Text] [PDF]

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