PDF(Pubmed)
Abstract：
Dystroglycan (DG) is a transmembrane protein widely expressed in multiple cells and tissues. It is formed by two subunits, α- and β-DG, and represents a molecular bridge between the outside and the inside of the cell, which is essential for the mechanical and structural stability of the plasma membrane. The α-subunit is a cell-surface protein that binds to the extracellular matrix (ECM) and is tightly associated with the plasma membrane via a non-covalent interaction with the β-subunit, which, in turn, is a transmembrane protein that binds to the cytoskeletal actin. DG is a versatile molecule acting not only as a mechanical building block but also as a modulator of outside-inside signaling events. The cytoplasmic domain of β-DG interacts with different adaptor and cytoskeletal proteins that function as molecular switches for the transmission of ECM signals inside the cells. These interactions can modulate the involvement of DG in different biological processes, ranging from cell growth and survival to differentiation and proliferation/regeneration. Although the molecular events that characterize signaling through the ECM-DG-cytoskeleton axis are still largely unknown, in recent years, a growing list of evidence has started to fill the gaps in our understanding of the role of DG in signal transduction. This mini-review represents an update of recent developments, uncovering the dual role of DG as an adhesion and signaling molecule that might inspire new ideas for the design of novel therapeutic strategies for pathologies such as muscular dystrophy, cardiomyopathy, and cancer, where the DG signaling hub plays important roles.
摘要：
Dystroglycan（DG）是一种在多种细胞和组织中广泛表达的跨膜蛋白。它由两个子单元组成，α-和β-DG，代表细胞外部和内部之间的分子桥，这对于质膜的机械和结构稳定性至关重要。α亚基是一种细胞表面蛋白，与细胞外基质（ECM）结合，并通过与β亚基的非共价相互作用与质膜紧密结合。which,反过来,是与细胞骨架肌动蛋白结合的跨膜蛋白。DG是一种多功能分子，不仅用作机械结构单元，而且还用作内外信号事件的调节剂。β-DG的细胞质结构域与不同的衔接子和细胞骨架蛋白相互作用，这些蛋白充当分子开关，用于在细胞内传递ECM信号。这些相互作用可以调节DG参与不同的生物过程，从细胞生长和存活到分化和增殖/再生。尽管表征通过ECM-DG-细胞骨架轴信号传导的分子事件在很大程度上仍然未知，近年来,越来越多的证据开始填补我们对DG在信号转导中的作用的理解空白。这个小型评论代表了最近的事态发展，揭示DG作为粘附和信号分子的双重作用，可能会激发设计新的治疗策略的新思路，心肌病,和癌症，其中DG信令集线器起着重要作用。
