Andrade Leonardo R
Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
Laboratory of Biomineralization, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil.
Cytoskeleton (Hoboken). 2015 Jun;72(6):282-91. doi: 10.1002/cm.21227. Epub 2015 Jun 30.
Cytoplasmic actin isoforms beta (β-) and gamma (γ-) perform crucial physiological roles in inner ear hair cells (HC). The stereocilium, which is structured by parallel actin filaments composed of both isoforms, is the responsive organelle to mechanical stimuli such as sound, gravity and head movements. Modifications in isoform proportions affect the function of the stereocilia as previously shown in genetic studies of mutant mice. Here, immunogold labeling TEM studies in mice showed that both β- and γ-actin isoforms colocalize throughout stereocilia actin filaments, adherens junctions and cuticular plates as early as embryonic stage 16.5. Gold-particle quantification indicated that there was 40% more γ- actin than β-actin at E16.5. In contrast, β- and γ-actin were equally concentrated in adult stereocilia of cochlear and vestibular HC. Interestingly, all actin-based structures presented almost five-fold more β-actin than γ-actin in 22 month- old mice, suggesting that γ-actin is probably under-expressed during the aging process. These data provide evidence of dynamic modifications of the actin isoforms in stereocilia, cuticular plates and cell junctions during the whole HC life.
细胞质肌动蛋白异构体β(β-)和γ(γ-)在内耳毛细胞(HC)中发挥着关键的生理作用。由这两种异构体组成的平行肌动蛋白丝构成的静纤毛,是对声音、重力和头部运动等机械刺激作出反应的细胞器。如先前在突变小鼠的基因研究中所示,异构体比例的改变会影响静纤毛的功能。在这里,对小鼠的免疫金标记透射电子显微镜研究表明,早在胚胎第16.5阶段,β-和γ-肌动蛋白异构体就共定位于整个静纤毛肌动蛋白丝、黏着连接和表皮板中。金颗粒定量分析表明,在胚胎第16.5阶段,γ-肌动蛋白比β-肌动蛋白多40%。相比之下,β-和γ-肌动蛋白在成年耳蜗和前庭毛细胞的静纤毛中浓度相等。有趣的是,在22月龄小鼠中,所有基于肌动蛋白的结构中β-肌动蛋白比γ-肌动蛋白多近五倍,这表明γ-肌动蛋白在衰老过程中可能表达不足。这些数据为整个毛细胞生命周期中静纤毛、表皮板和细胞连接中肌动蛋白异构体的动态变化提供了证据。