Responses to Cell Loss Become Restricted as the Supporting Cells in Mammalian Vestibular Organs Grow Thick Junctional Actin Bands That Develop High Stability
Responses to Cell Loss Become Restricted as the Supporting Cells in Mammalian Vestibular Organs Grow Thick Junctional Actin Bands That Develop High Stability
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DOI：
10.1523/jneurosci.4355-13.2014
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发表时间：
2014-01-29
影响因子：
5.3
通讯作者：
Corwin, Jeffrey T.
中科院分区：
文献类型：
--
作者：
Burns, Joseph C.;Corwin, Jeffrey T.
感觉毛细胞（HC）丢失是人类和其他哺乳动物永久性听力和平衡障碍的主要原因。然而，鱼类、两栖动物、爬行动物和鸟类很容易取代hc并从这种感觉缺陷中恢复过来。目前尚不清楚是什么阻止了哺乳动物的替代，但细胞替代能力下降的同时，出生后前庭支持细胞（SCs）连接处的f -肌动蛋白带大量增厚。在非哺乳动物中，SCs可以产生再生的hc，即使在成人中，条带仍然很薄。本文研究了鸡和小鼠耳内SCs与Madin-Darby犬肾细胞间f -肌动蛋白带的稳定性。表达γ -肌动蛋白- gfp融合蛋白的小鼠胞囊SC连接的药理学实验和光漂白后荧光恢复（FRAP）表明，增厚的f -肌动蛋白带具有增强的解聚抗性和卓越的稳定性，与成熟的哺乳动物耳朵细胞替代能力的急剧下降相似。FRAP回收率和γ -actin- gfp的流动分数随年龄的增长而下降，并趋于高度稳定。在新生小鼠的胞室中，死亡的hc附近的延时记录显示，许多sc改变形状并组织多细胞肌动蛋白包束，重新封闭上皮。相比之下，成年SCs似乎对变形有抵抗力，重新密封反应仅限于少数没有形成钱包的邻近SCs。成熟SCs连接处独特的厚f -肌动蛋白带的特殊稳定性可能在限制哺乳动物前庭上皮的动态修复反应中起重要作用。
Sensory hair cell (HC) loss is a major cause of permanent hearing and balance impairments for humans and other mammals. Yet, fish, amphibians, reptiles, and birds readily replace HCs and recover from such sensory deficits. It is unknown what prevents replacement in mammals, but cell replacement capacity declines contemporaneously with massive postnatal thickening of F-actin bands at the junctions between vestibular supporting cells (SCs). In non-mammals, SCs can give rise to regenerated HCs, and the bands remain thin even in adults. Here we investigated the stability of the F-actin bands between SCs in ears from chickens and mice and Madin-Darby canine kidney cells. Pharmacological experiments and fluorescence recovery after photobleaching (FRAP) of SC junctions in utricles from mice that express a gamma-actin-GFP fusion protein showed that the thickening F-actin bands develop increased resistance to depolymerization and exceptional stability that parallels a sharp decline in the cell replacement capacity of the maturing mammalian ear. The FRAP recovery rate and the mobile fraction of gamma-actin-GFP both decreased as the bands thickened with age and became highly stabilized. In utricles from neonatal mice, time-lapse recordings in the vicinity of dying HCs showed that numerous SCs change shape and organize multicellular actin purse strings that reseal the epithelium. In contrast, adult SCs appeared resistant to deformation, with resealing responses limited to just a few neighboring SCs that did not form purse strings. The exceptional stability of the uniquely thick F-actin bands at the junctions of mature SCs may play an important role in restricting dynamic repair responses in mammalian vestibular epithelia.