Septins guide noncentrosomal microtubules to promote focal adhesion disassembly in migrating cells.
Septins guide noncentrosomal microtubules to promote focal adhesion disassembly in migrating cells.
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DOI：
10.1091/mbc.e21-06-0334
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发表时间：
2022-05-01
影响因子：
3.3
通讯作者：
Myers, Kenneth A.
中科院分区：
文献类型：
--
作者：
Merenich, Daniel;Nakos, Konstantinos;Pompan, Taylor;Donovan, Samantha J.;Gill, Amrik;Patel, Pranav;Spiliotis, Elias T.;Myers, Kenneth A.
内皮细胞迁移对于血管生成至关重要，并且被损害以促进肿瘤转移。迁移过程需要粘着斑（FA），肌动蛋白和微管（MT）的协调组装和拆卸。MT动力学在FA提供囊泡货物和增强肌动球蛋白收缩，以促进FA周转，促进细胞前进。非中心体（NC）MT调节FA动力学，并足以驱动细胞极性，但NC MT如何靶向FA控制FA营业额还不清楚。在这里，我们表明，Rac 1诱导组装的FA近端隔蛋白丝，促进NC MT生长成FA和抑制有丝分裂着丝粒相关驱动蛋白（MCAK）相关的MT拆卸，从而保持完整的MT加上近端FA。Septin相关的MT拯救与Aurora-A激酶和细胞质接头相关蛋白（CLASP）定位于Septin和FA之间的MT的积累相结合。通过这种方式，NC MT被战略性地定位以经历MCAK和CLASP调节的装配和拆卸成FA的回合，从而调节FA周转和细胞迁移。
Endothelial cell migration is critical for vascular angiogenesis and is compromised to facilitate tumor metastasis. The migratory process requires the coordinated assembly and disassembly of focal adhesions (FA), actin, and microtubules (MT). MT dynamics at FAs deliver vesicular cargoes and enhance actomyosin contractility to promote FA turnover and facilitate cell advance. Noncentrosomal (NC) MTs regulate FA dynamics and are sufficient to drive cell polarity, but how NC MTs target FAs to control FA turnover is not understood. Here, we show that Rac1 induces the assembly of FA-proximal septin filaments that promote NC MT growth into FAs and inhibit mitotic centromere-associated kinesin (MCAK)-associated MT disassembly, thereby maintaining intact MT plus ends proximal to FAs. Septin-associated MT rescue is coupled with accumulation of Aurora-A kinase and cytoplasmic linker-associated protein (CLASP) localization to the MT between septin and FAs. In this way, NC MTs are strategically positioned to undergo MCAK- and CLASP-regulated bouts of assembly and disassembly into FAs, thereby regulating FA turnover and cell migration.
影响因子：
2.4
作者：
Myer NM;Myers KA
通讯作者：
Myers KA