CLASP1 regulates endothelial cell branching morphology and directed migration.
CLASP1 regulates endothelial cell branching morphology and directed migration.
复制标题
DOI：
10.1242/bio.028571
复制
发表时间：
2017-10-15
期刊：
影响因子：
2.4
通讯作者：
Myers KA
中科院分区：
文献类型：
--
作者：
Myer NM;Myers KA
内皮细胞 (EC) 分支严重依赖于微管 (MT) 细胞骨架的动态性质。细胞外基质（ECM）机械传感是实现细胞骨架重组的重要机制；然而，ECM 诱导的信号传导如何能够靶向细胞内的细胞骨架重组以促进高效的 EC 分支形态发生尚不清楚。在这里，我们测试了这样的假设：ECM 的组成和密度通过靶向 MT 稳定蛋白、细胞质连接相关蛋白 1 (CLASP1) 来驱动 EC 中 MT 生长动力学的调节。高分辨率荧光显微镜结合计算图像分析表明，CLASP1 促进玻璃 ECM 上的 MT 缓慢生长，并促进高密度 I 型胶原和纤连蛋白 ECM 上的短寿命 MT 生长。在 EC 分支内，高密度 I 型胶原蛋白或高密度纤连蛋白 ECM 的参与会导致 MT 生长速度降低，而 CLASP1 对 MT 动力学的依赖性效应会促进短分支突起数量的增加，从而引导 EC 持续和定向迁移。摘要：CLASP1 通过亚细胞特异性调节微管动力学，以响应细胞外基质密度和组成。 CLASP1 对微管的影响促进短的、分支的突起，引导 EC 的持续和定向迁移。作为补充信息的一部分，本文有与论文第一作者相关的第一人称采访。
Endothelial cell (EC) branching is critically dependent upon the dynamic nature of the microtubule (MT) cytoskeleton. Extracellular matrix (ECM) mechanosensing is a prominent mechanism by which cytoskeletal reorganization is achieved; yet how ECM-induced signaling is able to target cytoskeletal reorganization intracellularly to facilitate productive EC branching morphogenesis is not known. Here, we tested the hypothesis that the composition and density of the ECM drive the regulation of MT growth dynamics in ECs by targeting the MT stabilizing protein, cytoplasmic linker associated protein 1 (CLASP1). High-resolution fluorescent microscopy coupled with computational image analysis reveal that CLASP1 promotes slow MT growth on glass ECMs and promotes short-lived MT growth on high-density collagen-I and fibronectin ECMs. Within EC branches, engagement of either high-density collagen-I or high-density fibronectin ECMs results in reduced MT growth speeds, while CLASP1-dependent effects on MT dynamics promotes elevated numbers of short, branched protrusions that guide persistent and directed EC migration. Summary: CLASP1 modulates microtubule dynamics with sub-cellular specificity in response to extracellular matrix density and composition. CLASP1 effects on microtubules promote short, branched protrusions that guide persistent and directional EC migration. This article has an associated First Person interview with the first author of the paper as part of the supplementary information.
登录
查看更多内容
DOI：
10.3791/54265
发表时间：
2016-08-13
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Braun A;Caesar NM;Dang K;Myers KA
通讯作者：
Myers KA
影响因子：
5.3
作者：
Dent, EW;Kalil, K
通讯作者：
Kalil, K
影响因子：
64.5
作者：
Akhmanova, A;Hoogenraad, CC;Galjart, N
通讯作者：
Galjart, N
影响因子：
11.8
作者：
Al-Bassam, Jawdat;Kim, Hwajin;Brouhard, Gary;van Oijen, Antoine;Harrison, Stephen C.;Chang, Fred
通讯作者：
Chang, Fred
影响因子：
3.3
作者：
D'Angelo, Lauren;Myer, Nicole M.;Myers, Kenneth A.
通讯作者：
Myers, Kenneth A.