Toward an understanding of cochlear homeostasis: the impact of location and the role of OCP1 and OCP2.
Toward an understanding of cochlear homeostasis: the impact of location and the role of OCP1 and OCP2.
复制标题
了解耳蜗稳态：位置的影响以及 OCP1 和 OCP2 的作用。
DOI：
10.1080/0036554021000028100
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发表时间：
2003
影响因子：
1.4
通讯作者：
Thalmann,Isolde
中科院分区：
文献类型：
--
作者：
Thalmann,Ruediger;Henzl,MichaelT;Killick,Richard;Ignatova,ElenaG;Thalmann,Isolde
支持细胞群或上皮支持复合物 (ESC) 在耳蜗稳态中的核心作用已获得普遍认可。然而，这一角色的细节可能会因地点的不同而有显着差异，但人们仍然对此知之甚少。例如，K+再循环路径很可能由沿耳蜗轴的位置决定：靠近顶点的外淋巴路径和靠近基部的跨细胞路径。 ESC 表达非常高水平的 OCP1 和 OCP2，目前已知它们是新型柯蒂器官 (OC) 特异性 SCF 泛素连接酶 (SCFOCP1) 的组成部分。在 SCFOCP1 复合物中，OCP1 可能结合选定的蛋白质靶标，将它们定位为泛素化。最近重组 OCP1 与 Cx26 非共价相互作用的证明表明连接蛋白可能是 SCFOCP1 的靶蛋白。尽管泛素化传统上被视为 26S 蛋白酶体随后破坏的信号，但 OC 的能量有限状态促使人们考虑其他命运，例如可逆的内化。 ESC 还表达 Wingless/Wnt 信号通路的多个组件。值得注意的是，OC 中表达的两种间隙连接蛋白 Cx43 和 Cx30 是 Wnt 通路的已知靶标。基于这些观察结果，提出了一个工作假设，其中 Wnt 通路激活连接蛋白表达，而 OCP1 调节其降解。
The central role of the supporting cell population, or epithelial support complex (ESC), in cochlear homeostasis has gained general acceptance. That the details of this role may vary markedly with location, however, remains poorly appreciated. For example, the K+recirculation pathway may well be dictated by position along the cochlear axis: a perilymphatic route near the apex and a transcellular one near the base. The ESC expresses very high levels of OCP1 and OCP2, now known to be components of a novel, organ of Corti (OC)-specific SCF ubiquitin ligase (SCFOCP1). In the SCFOCP1complex, OCP1 presumably binds selected protein targets, positioning them for ubiquitination. The recent demonstration that recombinant OCP1 interacts non-covalently with Cx26 suggests that the connexins may be target proteins for SCFOCP1. Although ubiquitination has classically been viewed as a signal for subsequent destruction by the 26S proteasome, the energy-limited state of the OC prompts consideration of alternative fates, e.g. reversible internalization. The ESC also expresses several components of the Wingless/Wnt signaling pathway. Significantly, two of the gap-junction proteins expressed in the OC, Cx43 and Cx30, are known targets of the Wnt pathway. On the basis of these observations, a working hypothesis is proposed wherein the Wnt pathway activates connexin expression, while OCP1 regulates its degradation.