title: Gelsolin plays a role in the actin polymerization complex of hair cell stereocilia.
abstract: A complex of proteins scaffolded by the PDZ protein, whirlin, reside at the stereocilia tip and are critical for stereocilia development and elongation. We have shown that in outer hair cells (OHCs) whirlin is part of a larger complex involving the MAGUK protein, p55, and protein 4.1R. Whirlin interacts with p55 which is expressed exclusively in outer hair cells (OHC) in both the long stereocilia that make up the stereocilia bundle proper as well as surrounding shorter microvilli that will eventually regress. In erythrocytes, p55 forms a tripartite complex with protein 4.1R and glycophorin C promoting the assembly of actin filaments and the interaction of whirlin with p55 indicates that it plays a similar role in OHC stereocilia. However, the components directly involved in actin filament regulation in stereocilia are unknown. We have investigated additional components of the whirlin interactome by identifying interacting partners to p55. We show that the actin capping and severing protein, gelsolin, is a part of the whirlin complex. Gelsolin is detected in OHC where it localizes to the tips of the shorter rows but not to the longest row of stereocilia and the pattern of localisation at the apical hair cell surface is strikingly similar to p55. Like p55, gelsolin is ablated in the whirler and shaker2 mutants. Moreover, in a gelsolin mutant, stereocilia in the apex of the cochlea become long and straggly indicating defects in the regulation of stereocilia elongation. The identification of gelsolin provides for the first time a link between the whirlin scaffolding protein complex involved in stereocilia elongation and a known actin regulatory molecule.
authors.affiliation: Medical Research Council Mammalian Genetics Unit, Harwell Science and Innovation Campus, Oxfordshire, United Kingdom.
authors.forename: Philomena
authors.initials: P
authors.lastname: Mburu
authors.forename: María Rosario
authors.initials: MR
authors.lastname: Romero
authors.forename: Helen
authors.initials: H
authors.lastname: Hilton
authors.forename: Andrew
authors.initials: A
authors.lastname: Parker
authors.forename: Stuart
authors.initials: S
authors.lastname: Townsend
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kikkawa
authors.forename: Steve D M
authors.initials: SD
authors.lastname: Brown
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002853:Chromatography, Liquid; D002923:Cilia / Q000235:genetics / Q000378:metabolism*; D018260:Gelsolin / Q000235:genetics / Q000378:metabolism*; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000378:metabolism* / Q000648:ultrastructure; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008855:Microscopy, Electron, Scanning; D009218:Myosins / Q000235:genetics / Q000502:physiology; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D053719:Tandem Mass Spectrometry
chemical_list: D000199:Actins; D018260:Gelsolin; C114013:Myo15 protein, mouse; D051528:Guanylate Kinases; D009218:Myosins