Signaling pathways and the cerebral cavernous malformations proteins: lessons from structural biology.
Signaling pathways and the cerebral cavernous malformations proteins: lessons from structural biology.
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DOI：
10.1007/s00018-013-1532-9
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发表时间：
2014-05
影响因子：
8
通讯作者：
Boggon, Titus J.
中科院分区：
文献类型：
--
作者：
Fisher, Oriana S.;Boggon, Titus J.
关键词：
脑海绵状血管畸形（CCM）是一种神经血管发育不良，导致主要位于脑和脊髓组织中的桑葚状病变。三个基因的突变与CCM相关。这些基因编码蛋白质KRIT 1/CCM 1（krev相互作用捕获1/脑海绵状畸形1）、脑海绵状畸形2、MEKK 3（CCM 2/malcavernin/OSM）和脑海绵状畸形3/程序性细胞死亡10（CCM 3/PDCD 10）。在我们对这些蛋白质的结构和功能以及它们在细胞信号传导中的作用的理解方面，最近有许多重大进展。在这里，我们提供了一个更新的CCM蛋白的结构和它们的功能在细胞信号转导，特别是在细胞粘附复合物和信号级联的现有知识。我们继续讨论CCM蛋白的亚细胞定位，CCM复合物信号平台的形成和调节，以及CCM疾病靶向治疗的最新进展。最近的结构研究已经开始为CCM蛋白的功能提供新的线索，我们在这里重点介绍这些研究如何帮助了解目前对这些作用的理解，以及它们如何有助于未来对CCM相关生物学和疾病机制的研究。
Cerebral cavernous malformations (CCM) are neurovascular dysplasias that result in mulberry-shaped lesions predominantly located in brain and spinal tissues. Mutations in three genes are associated with CCM. These genes encode for the proteins KRIT1/CCM1 (krev interaction trapped 1/cerebral cavernous malformations 1), cerebral cavernous malformations 2, osmosensing scaffold for MEKK3 (CCM2/malcavernin/OSM), and cerebral cavernous malformations 3/programmed cell death 10 (CCM3/PDCD10). There have been many significant recent advances in our understanding of the structure and function of these proteins, as well as in their roles in cellular signaling. Here, we provide an update on the current knowledge of the structure of the CCM proteins and their functions within cellular signaling, particularly in cellular adhesion complexes and signaling cascades. We go on to discuss subcellular localization of the CCM proteins, the formation and regulation of the CCM complex signaling platform, and current progress towards targeted therapy for CCM disease. Recent structural studies have begun to shed new light on CCM protein function, and we focus here on how these studies have helped inform the current understanding of these roles and how they may aid future studies into both CCM-related biology and disease mechanisms.
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影响因子：
4.8
作者：
Borikova, Asya L.;Dibble, Christopher F.;Johnson, Gary L.
通讯作者：
Johnson, Gary L.
影响因子：
4.6
作者：
Bouvard, Daniel;Aszodi, Attila;Faessler, Reinhard
通讯作者：
Faessler, Reinhard
影响因子：
20.1
作者：
Bruetsch, Rene;Liebler, Sven S.;Fischer, Andreas
通讯作者：
Fischer, Andreas
影响因子：
21.3
作者：
Boettcher, Ralph Thomas;Stremmel, Christopher;Faessler, Reinhard
通讯作者：
Faessler, Reinhard
影响因子：
4.8
作者：
Bouvard, D;Vignoud, L;Block, MR
通讯作者：
Block, MR