Absence of plastin 1 causes abnormal maintenance of hair cell stereocilia and a moderate form of hearing loss in mice.
Bottom Line: Auditory hair cells developed normally in Pls1 KO, but in young adult animals, the stereocilia of inner hair cells were reduced in width and length.These results show that in contrast to other actin-bundling proteins such as espin, harmonin or Eps8, plastin 1 is dispensable for the initial formation of stereocilia.Hence, mutations in the human PLS1 gene may be associated with relatively mild and progressive forms of hearing loss.
Affiliation: Centre for Auditory Research, UCL Ear Institute, University College London, London, UK.Show MeSH
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Mentions: Like microvilli, the stereocilia contain a central core of densely packed parallel actin filaments of the same polarity, the number and length of which vary proportionally to stereocilia size (2–5). This actin core is thought to confer rigidity to stereocilia, which upon mechanical stimulation behave like stiff rods that pivot around their tapered base (6,7). Three classes of actin-bundling proteins, belonging to the espin, fascin and plastin families, are present in stereocilia. Distinct espin isoforms are expressed in developing and mature stereocilia (8), and mutations in the ESPN/Espn gene cause a profound form of congenital deafness in humans (9,10) and in jerker mice (11). In the absence of espin, stereocilia fail to widen and degenerate soon after their initial formation, suggesting that espin is required for the lateral apposition of parallel actin bundles within stereocilia and their consequent increase in diameter (12,13). Fascin2 appears during the final stages of stereocilia elongation and is concentrated at the tips of the taller stereocilia (14). Mutations of the Fscn2 gene cause a progressive degeneration of stereocilia and an early onset age-related hearing loss (ahl8) in DBA/2J mice, which also carry a mutation in cadh23 (14). Of the plastins, plastin 3 is transiently expressed during the formation of stereocilia in immature hair cells (15), whereas plastin 1, the homologue of chicken fimbrin (16), is present in the stereocilia and cuticular plate of developing and mature hair cells (Fig. 1 and Supplementary Material, Fig. S1) (17–21). Biochemical studies have shown that plastin 1 is one of the most abundant proteins of stereocilia (14,22,23), yet its actual contribution to stereocilia formation and function has not been directly assessed.Figure 1.
Affiliation: Centre for Auditory Research, UCL Ear Institute, University College London, London, UK.