Extracellular chloride signals collagen IV network assembly during basement membrane formation.
Extracellular chloride signals collagen IV network assembly during basement membrane formation.
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细胞外氯化物在基底膜形成过程中发出胶原 IV 网络组装信号
DOI：
10.1083/jcb.201510065
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发表时间：
2016-05-23
期刊：
影响因子：
--
通讯作者：
Hudson BG
中科院分区：
文献类型：
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作者：
Cummings CF;Pedchenko V;Brown KL;Colon S;Rafi M;Jones-Paris C;Pokydeshava E;Liu M;Pastor-Pareja JC;Stothers C;Ero-Tolliver IA;McCall AS;Vanacore R;Bhave G;Santoro S;Blackwell TS;Zent R;Pozzi A;Hudson BG
氯化物在生理学中普遍存在，但被理解为提供组织功能的离子强度。作者发现了氯离子的分子功能，由此离子发出胶原IV组装的信号，在细胞外部建立微环境。基底膜是细胞微环境的定义特征;然而，关于它们在细胞外的组装知之甚少。我们报告说，细胞外的Cl−离子信号的组装胶原蛋白IV网络细胞外的触发内胶原蛋白IV非胶原蛋白1（NC 1）结构域的构象开关。细胞培养中Cl−的耗尽扰乱了胶原IV网络，破坏了基质结构，并重新定位了基底膜蛋白。系统发育证据表明这种构象转换是后生动物中IV型胶原网络组装的基本机制。使用重组三螺旋原聚体，我们证明，NC 1域直接原聚体和网络组装和显示在果蝇中，NC 1架构是至关重要的纳入基底膜。这些发现提供了对细胞外Cl−和细胞外胶原IV组装之间动态相互作用的原子水平理解，这是基底膜组装和组织的关键步骤，使组织结构和功能成为可能。此外，这为理解NC 1结构域的分子病理学提供了一个机制框架。
Chloride is ubiquitous in physiology but understood to provide ionic strength for tissue function. The authors discover a molecular function of chloride whereby the ion signals the assembly of collagen IV, establishing a microenvironment on the outside of cells. Basement membranes are defining features of the cellular microenvironment; however, little is known regarding their assembly outside cells. We report that extracellular Cl− ions signal the assembly of collagen IV networks outside cells by triggering a conformational switch within collagen IV noncollagenous 1 (NC1) domains. Depletion of Cl− in cell culture perturbed collagen IV networks, disrupted matrix architecture, and repositioned basement membrane proteins. Phylogenetic evidence indicates this conformational switch is a fundamental mechanism of collagen IV network assembly throughout Metazoa. Using recombinant triple helical protomers, we prove that NC1 domains direct both protomer and network assembly and show in Drosophila that NC1 architecture is critical for incorporation into basement membranes. These discoveries provide an atomic-level understanding of the dynamic interactions between extracellular Cl− and collagen IV assembly outside cells, a critical step in the assembly and organization of basement membranes that enable tissue architecture and function. Moreover, this provides a mechanistic framework for understanding the molecular pathobiology of NC1 domains.