ADP-ribosylation factor 6 regulates mammalian myoblast fusion through phospholipase D1 and phosphatidylinositol 4,5-bisphosphate signaling pathways.
ADP-ribosylation factor 6 regulates mammalian myoblast fusion through phospholipase D1 and phosphatidylinositol 4,5-bisphosphate signaling pathways.
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DOI：
10.1091/mbc.e09-12-1063
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发表时间：
2010-07-15
影响因子：
3.3
通讯作者：
Gauthier-Rouvière C
中科院分区：
文献类型：
--
作者：
Bach AS;Enjalbert S;Comunale F;Bodin S;Vitale N;Charrasse S;Gauthier-Rouvière C
在这里，我们表明ARF 6与包含M-钙粘蛋白、Trio和Rac 1的多蛋白复合物相关，并在成肌细胞融合位点积聚。ARF 6沉默抑制Trio和Rac 1与M-钙粘蛋白的结合。此外，我们证明ARF 6通过磷脂酶D激活和PI（4，5）P2产生调节成肌细胞融合。成肌细胞融合是成肌细胞分化过程中的一个重要步骤，但目前对其了解甚少。通过Rho-鸟嘌呤核苷酸交换因子（GEF）Trio激活Rac 1 GTdR的M-钙粘蛋白依赖性通路对成肌细胞融合很重要。ADP-核糖基化因子（ARF）6 GTdR已显示与Trio结合并调节Rac 1活性。此外，作为ARF 6的GEF，Loner/GEP 100/BRAG 2参与了哺乳动物和果蝇成肌细胞的融合，但ARF 6的具体作用尚未完全分析。在这里，我们表明，ARF 6活性增加的时候，成肌细胞融合，并需要其实施在小鼠C2 C12成肌细胞。具体而言，在成肌细胞融合开始时，ARF 6与含有M-钙粘蛋白、Trio和Rac 1的多蛋白复合物相关，并在成肌细胞融合部位积累。ARF 6沉默抑制Trio和Rac 1与M-钙粘蛋白的结合。此外，我们证明，ARF 6调节成肌细胞融合通过磷脂酶D（PLD）的激活和磷脂酰肌醇4，5-二磷酸生产。总之，这些数据表明，ARF 6是C2 C12成肌细胞融合的关键调节因子，并参与调节PLD活性，从而触发融合位点的磷脂产生和肌动蛋白细胞骨架重组。
Here we show that ARF6 is associated with the multiproteic complex that contains M-cadherin, Trio, and Rac1 and accumulates at sites of myoblast fusion. ARF6 silencing inhibits the association of Trio and Rac1 with M-cadherin. Moreover, we demonstrate that ARF6 regulates myoblast fusion through Phospholipase D activation and PI(4,5)P2 production. Myoblast fusion is an essential step during myoblast differentiation that remains poorly understood. M-cadherin–dependent pathways that signal through Rac1 GTPase activation via the Rho-guanine nucleotide exchange factor (GEF) Trio are important for myoblast fusion. The ADP-ribosylation factor (ARF)6 GTPase has been shown to bind to Trio and to regulate Rac1 activity. Moreover, Loner/GEP100/BRAG2, a GEF of ARF6, has been involved in mammalian and Drosophila myoblast fusion, but the specific role of ARF6 has been not fully analyzed. Here, we show that ARF6 activity is increased at the time of myoblast fusion and is required for its implementation in mouse C2C12 myoblasts. Specifically, at the onset of myoblast fusion, ARF6 is associated with the multiproteic complex that contains M-cadherin, Trio, and Rac1 and accumulates at sites of myoblast fusion. ARF6 silencing inhibits the association of Trio and Rac1 with M-cadherin. Moreover, we demonstrate that ARF6 regulates myoblast fusion through phospholipase D (PLD) activation and phosphatidylinositol 4,5-bis-phosphate production. Together, these data indicate that ARF6 is a critical regulator of C2C12 myoblast fusion and participates in the regulation of PLD activities that trigger both phospholipids production and actin cytoskeleton reorganization at fusion sites.
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影响因子：
9.2
作者：
Estrach, S;Schmidt, S;Debant, A
通讯作者：
Debant, A
影响因子：
16.2
作者：
Grishanin, RN;Kowalchyk, JA;Martin, TFJ
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Martin, TFJ
影响因子：
4.6
作者：
Causeret, F;Hidalgo-Sanchez, M;Bloch-Gallego, E
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Bloch-Gallego, E
影响因子：
12.4
作者：
Fortier, M.;Comunale, F.;Gauthier-Rouviere, C.
通讯作者：
Gauthier-Rouviere, C.
影响因子：
64.8
作者：
Hakeda-Suzuki, S;Ng, J;Dickson, BJ
通讯作者：
Dickson, BJ