Stereocilia formation and maintenance

Stereocilia are microvilli-like structures arranged into a neat bundle at the surface of each hair cell. When fluid movements occur in the liquid-filled compartments of the inner ear, stereocilia are displaced, triggering the release of neurotransmitters by hair cells. Mutations in genes encoding molecular components of the stereocilia are frequently associated to hereditary forms of deafness. Our work has uncovered a specific function for an actin-bundling protein named Plastin1 (also known as Fimbrin) in the maintenance of auditory hair cell stereocilia. In mice deficient for the Plastin1 gene, the stereocilia form normally but rapidly become 'floppy' - suggesting that the actin filaments that form the backbone of stereocilia are not properly maintained. These mice become progressively deaf, although we do not know (yet) if the Plastin1 gene is associated to similar hearing problems in humans.

Collaborators: A. Bullen, A. Forge, R. Taylor (Ear Institute), F. Rivero (U. of Hull), S. Johnson, W. Marcotti (U. of Sheffield), M. Davey (University of Edinburgh)

Publications:

• Taylor, R., Bullen, A., Johnson, S.L., Grimm-Günter, E.M., Rivero, F., Marcotti, W., Forge, A. and Daudet, N. (2015). Absence of plastin 1 causes abnormal maintenance of hair cell stereocilia and a moderate form of hearing loss in mice.. Human Molecular Genetics, 24 (1), 37-49. doi:10.1093/hmg/ddu417
• Stephen, L.A., Tawamie, H., Davis, G.M., Tebbe, L., Nürnberg, P., Nürnberg, G., ...Uebe, S. (2015). TALPID3 controls centrosome and cell polarity and the human ortholog KIAA0586 is mutated in Joubert syndrome ( JBTS23 ). eLife, 4 doi:10.7554/eLife.08077