Definition of the fibroblast adhesome using multiplexed proximity biotinylation
Definition of the fibroblast adhesome using multiplexed proximity biotinylation
复制标题
DOI：
10.1101/2020.01.24.918458
复制
发表时间：
2020-01
期刊：
影响因子：
--
通讯作者：
Megan R. Chastney;C. Lawless;J. Humphries;Stacey Warwood;Matthew C. Jones;David Knight;Claus Jørgensen;M. Humphries
中科院分区：
文献类型：
--
作者：
Megan R. Chastney;C. Lawless;J. Humphries;Stacey Warwood;Matthew C. Jones;David Knight;Claus Jørgensen;M. Humphries
整合素粘附复合物（IACs）在细胞外基质与肌动蛋白细胞骨架之间架起桥梁，并根据化学和机械信号传导信号。IACs内蛋白质的组成、相互作用、化学计量学和拓扑结构尚不完全清楚。为了解决这一差距，我们使用多路邻近生物素化（BioID）在小鼠胰腺成纤维细胞中原位生成邻近依赖性粘附体。整合16个iac相关诱饵的相互作用组揭示了147个蛋白质的网络，其中有361个邻近相互作用。除了确定的IAC成分外，还确定了粘附作用未被充分认识的候选成分。生物信息学分析揭示了与常见猎物群体相关联的五类IAC诱饵，因此它们可能代表功能模块。这五个集群及其空间关联与当前IAC相互作用网络和分层模型一致。本研究提供了一种资源，可以在全球范围内检查IACs内部的近端关系。
Integrin adhesion complexes (IACs) bridge the extracellular matrix to the actin cytoskeleton and transduce signals in response to both chemical and mechanical cues. The composition, interactions, stoichiometry and topological organisation of proteins within IACs are not fully understood. To address this gap, we used multiplexed proximity biotinylation (BioID) to generate an in situ, proximity-dependent adhesome in mouse pancreatic fibroblasts. Integration of the interactomes of 16 IAC-associated baits revealed a network of 147 proteins with 361 proximity interactions. Candidates with underappreciated roles in adhesion were identified, in addition to established IAC components. Bioinformatic analysis revealed five clusters of IAC baits that link to common groups of prey, and which therefore may represent functional modules. The five clusters, and their spatial associations, are consistent with current models of IAC interaction networks and stratification. This study provides a resource to examine proximal relationships within IACs at a global level.