Inversin, Wnt signaling and primary cilia
Inversin, Wnt signaling and primary cilia
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DOI：
10.1016/j.diff.2011.11.012
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发表时间：
2012-02-01
期刊：
影响因子：
2.9
通讯作者：
Walz, Gerd
中科院分区：
文献类型：
--
作者：
Lienkamp, Soeren;Ganner, Athina;Walz, Gerd
锚蛋白重复蛋白 Inversin 是由超过 12 种蛋白质组成的不同家族的成员之一，其突变会导致肾痨 (NPH)，这是一种常染色体隐性遗传性囊性肾病，与色素性视网膜炎、小脑发育不全和内脏逆位等肾外表现相关。大多数 NPH 基因产物 (NPHP) 定位于纤毛，并且似乎通过形成功能网络来控制货物蛋白向纤毛的运输。 Inversin 与 NPHP1 和 NPHP3 相互作用，并与 NPHP4 共享拮抗 Dishevelled 刺激的经典 Wnt 信号传导的能力，可能是通过招募后期促进复合物 (APC/C)。然而，蓬乱的拮抗作用可能仅限于基体，从而使腹侧结和呼吸道细胞上的运动纤毛极化。 Inversin 对于响应激活的 Frizzled 将 Disheveled 招募到质膜至关重要，这是平面细胞极性信号传导的关键步骤。在脊椎动物前肾发育过程中，Inversin 介导的 Disheveled 易位似乎协调了细胞的迁移和与哺乳动物亨利环相对应的片段的分化。因此，有缺陷的肾小管迁移和伸长可能会导致 NPH 患者浓度缺陷并导致囊肿形成。 (C) 2011 年国际分化学会。由 Elsevier B.V. 出版。保留所有权利。
Mutations of the ankyrin-repeat protein Inversin, a member of a diverse family of more than 12 proteins, cause nephronophthisis (NPH), an autosomal recessive cystic kidney disease associated with extra-renal manifestations such as retinitis pigmentosa, cerebellar aplasia and situs inversus. Most NPH gene products (NPHPs) localize to the cilium, and appear to control the transport of cargo protein to the cilium by forming functional networks. Inversin interacts with NPHP1 and NPHP3, and shares with NPHP4 the ability to antagonize Dishevelled-stimulated canonical Wnt signaling, potentially through recruitment of the Anaphase Promoting Complex (APC/C). However, Dishevelled antagonism may be confined towards the basal body, thereby polarizing motile cilia on the cells of the ventral node and respiratory tract. Inversin is essential for recruiting Dishevelled to the plasma membrane in response to activated Frizzled, a crucial step in planar cell polarity signaling. During vertebrate pronephros development, the Inversin-mediated translocation of Dishevelled appears to orchestrate the migration of cells and differentiation of segments that correspond to the mammalian loop of Henle. Thus, defective tubule migration and elongation may contribute to concentration defects and cause cyst formation in patients with NPH. (C) 2011 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.