Actin Filament Formation in Myofibrils and Cell Protrusions Regulated by Signal Transduction
Actin Filament Formation in Myofibrils and Cell Protrusions Regulated by Signal Transduction
复制标题
信号转导调节的肌原纤维和细胞突起中肌动蛋白丝的形成
DOI：
10.1007/978-4-431-55561-2_18
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
K.
中科院分区：
文献类型：
--
作者：
Endo;T. and Takano;K.
肌动蛋白丝在所有真核细胞类型中的多种细胞功能中起着至关重要的作用。通常，它们作为可收缩肌原纤维的细丝对于肌肉收缩是必需的，并且作为应力纤维、丝状伪足和板状伪足的组分对于细胞迁移是必需的。特定的肌动蛋白成核因子和延伸因子参与肌动蛋白丝的形成，这取决于细胞类型和含有肌动蛋白的结构。肌动蛋白丝的形成以及它们的动力学是由复杂的信号机制调节的。本文综述了肌原纤维和细胞丝中肌动蛋白丝形成的分子和信号机制，这是一种参与细胞间信号传导的特殊类型的细胞突起，重点介绍了我们最近在这方面的研究。肌原纤维是众所周知的肌肉收缩结构，主要由肌动蛋白和肌球蛋白丝组成。然而，其形成的分子和信号机制一直是模糊的。我们阐明了胰岛素样生长因子1（IGF-1）诱导骨骼肌肌原纤维肌动蛋白丝形成的机制。IGF-1刺激的磷脂酰肌醇3-激酶-Akt信号传导诱导形成星云蛋白-N-WASP复合物，其使肌动蛋白成核并从Z带形成肌动蛋白丝。我们还研究了心肌中肌原纤维肌动蛋白丝形成的机制，其中星云蛋白是缺席的。另一方面，cytonemes代表了新的高效，长距离的细胞间信号传导机制。我们已经发现成纤维细胞生长因子信号传导引起RhoD的活化，其进而活化mDia 3C以形成肌动蛋白丝，从而导致细胞丝形成。
Actin filaments play crucial roles in a wide variety of cellular functions in all eukaryotic cell types. Typically, they are essential for muscle contraction as thin filaments of contractile myofibrils and for cell migration as components of stress fibers, filopodia, and lamellipodia. Specific actin nucleation factors and elongation factors participate in actin filament formation depending on cell types and actin filament-containing structures. The formation of actin filaments as well as their dynamics is regulated by complicated signaling mechanisms. We summarize here molecular and signaling mechanisms of actin filament formation of myofibrils and cytonemes, a special type of cell protrusions involved in intercellular signaling, focusing on our recent research on these subjects. Myofibrils are well-known muscle contractile structures consisting mainly of actin and myosin filaments. However, molecular and signaling mechanisms of their formation have been obscure. We have elucidated the mechanisms of skeletal muscle myofibrillar actin filament formation induced by insulin-like growth factor 1 (IGF-1). IGF-1-stimulated phosphatidylinositol 3-kinase–Akt signaling induces the formation of the nebulin–N-WASP complex, which nucleates actin and forms actin filaments from the Z-bands. We have also examined the mechanisms of myofibrillar actin filament formation in cardiac muscle, in which nebulin is absent. On the other hand, cytonemes represent novel highly efficient, long-range intercellular signaling machinery. We have found that fibroblast growth factor signaling causes activation of RhoD, which in turn activates mDia3C to form actin filaments leading to cytoneme formation.