FHOD1 is a combined actin filament capping and bundling factor that selectively associates with actin arcs and stress fibers
FHOD1 is a combined actin filament capping and bundling factor that selectively associates with actin arcs and stress fibers
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DOI：
10.1242/jcs.126706
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发表时间：
2013-04-15
影响因子：
4
通讯作者：
Geyer, Matthias
中科院分区：
文献类型：
--
作者：
Schoenichen, Andre;Mannherz, Hans Georg;Geyer, Matthias
Formins是肌动蛋白聚合因子，已知在有刺端形成和拉长肌动蛋白丝。在本研究中，我们发现人类FHOD1缺乏肌动蛋白成核和延伸能力，但作为肌动蛋白捆绑因子，在丝的倒刺端具有旋盖活性。组成型活性FHOD1与丝状足和板足前缘的肌动蛋白丝相关，并随肌动蛋白逆行流动移动。在板足基部，FHOD1在新生的、捆绑的肌动蛋白弧线以及更成熟的应力纤维中富集。该功能需要位于典型FH1-FH2元件n端的动作蛋白结合结构域。在原肌凝蛋白存在的情况下，束状表型保持不变，通过电子显微镜证实，5到10个肌动蛋白丝组装成平行的、紧密间隔的丝束。综上所述，我们的数据表明，FHOD1通过保护其二聚体FH2结构域的刺端不被解聚来稳定肌动蛋白丝，而FH1结构域的n端区域通过同时结合到相邻的f -肌动蛋白丝的两侧来介导f -肌动蛋白的捆绑。
Formins are actin polymerization factors that are known to nucleate and elongate actin filaments at the barbed end. In the present study we show that human FHOD1 lacks actin nucleation and elongation capacity, but acts as an actin bundling factor with capping activity toward the filament barbed end. Constitutively active FHOD1 associates with actin filaments in filopodia and lamellipodia at the leading edge, where it moves with the actin retrograde flow. At the base of lamellipodia, FHOD1 is enriched in nascent, bundled actin arcs as well as in more mature stress fibers. This function requires actin-binding domains located N-terminally to the canonical FH1-FH2 element. The bundling phenotype is maintained in the presence of tropomyosin, confirmed by electron microscopy showing assembly of 5 to 10 actin filaments into parallel, closely spaced filament bundles. Taken together, our data suggest a model in which FHOD1 stabilizes actin filaments by protecting barbed ends from depolymerization with its dimeric FH2 domain, whereas the region N-terminal to the FH1 domain mediates F-actin bundling by simultaneously binding to the sides of adjacent F-actin filaments.