FHOD1 regulates stress fiber organization by controlling the dynamics of transverse arcs and dorsal fibers
FHOD1 regulates stress fiber organization by controlling the dynamics of transverse arcs and dorsal fibers
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DOI：
10.1242/jcs.134627
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发表时间：
2014-04-01
影响因子：
4
通讯作者：
Nalbant, Perihan
中科院分区：
文献类型：
--
作者：
Schulze, Nina;Graessl, Melanie;Nalbant, Perihan
在体外，FHOD1（含同源性2结构域的蛋白1）可以作为加帽和捆绑蛋白。在细胞中，活跃的FHOD1刺激腹侧应力纤维的形成。然而，这种表型产生的细胞机制和FHOD1功能的生理相关性目前还不清楚。在这里，我们首先表明，FHOD1控制两个不同的应力纤维前体的差异形成。一方面，它抑制背侧纤维的生长，这需要长的肌动蛋白丝的平行束的聚合。另一方面，它刺激由短的反平行肌动蛋白丝融合形成的横向弧。这种联合作用对于应力纤维的成熟及其时空组织是至关重要的，并且缺乏FHOD1功能会扰乱细胞迁移期间的动态细胞行为。此外，我们表明，GTP酶结合和同源性3域（GBD和FH 3）负责应力纤维协会和共定位与肌球蛋白。令人惊讶的是，缺乏这些结构域的FHOD1版本仍然保留了刺激弧和腹侧应力纤维形成的全部能力。基于我们的研究结果，我们提出了一种机制，其中FHOD1促进短肌动蛋白丝的形成，并短暂地与横向弧，从而提供严格的时间和空间控制的横向弧的形成和营业额在动态细胞行为成熟的腹侧应力纤维。
The formin FHOD1 (formin homology 2 domain containing protein 1) can act as a capping and bundling protein in vitro. In cells, active FHOD1 stimulates the formation of ventral stress fibers. However, the cellular mechanisms by which this phenotype is produced and the physiological relevance of FHOD1 function are not currently understood. Here, we first show that FHOD1 controls the formation of two distinct stress fiber precursors differentially. On the one hand, it inhibits dorsal fiber growth, which requires the polymerization of parallel bundles of long actin filaments. On the other hand, it stimulates transverse arcs that are formed by the fusion of short antiparallel actin filaments. This combined action is crucial for the maturation of stress fibers and their spatio-temporal organization, and a lack of FHOD1 function perturbs dynamic cell behavior during cell migration. Furthermore, we show that the GTPase-binding and formin homology 3 domains (GBD and FH3) are responsible for stress fiber association and colocalization with myosin. Surprisingly, a version of FHOD1 that lacks these domains nevertheless retains its full capacity to stimulate arc and ventral stress fiber formation. Based on our findings, we propose a mechanism in which FHOD1 promotes the formation of short actin filaments and transiently associates with transverse arcs, thus providing tight temporal and spatial control of the formation and turnover of transverse arcs into mature ventral stress fibers during dynamic cell behavior.