Howard Hughes Medical Institute, Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
G3 (Bethesda). 2013 Feb;3(2):251-62. doi: 10.1534/g3.112.005314. Epub 2013 Feb 1.
Dishevelled (Dsh or Dvl) is an important signaling protein, playing a key role in Wnt signaling and relaying cellular information for several developmental pathways. Dsh is highly conserved among metazoans and has expanded into a multigene family in most bilaterian lineages, including vertebrates, planarians, and nematodes. These orthologs, where explored, are known to have considerable overlap in function, but evidence for functional specialization continues to mount. We performed a comparative analysis of Dsh across animals to explore protein architecture and identify conserved and divergent features that could provide insight into functional specialization with an emphasis on invertebrates, especially nematodes. We find evidence of dynamic evolution of Dsh, particularly among nematodes, with taxa varying in ortholog number from one to three. We identify a new domain specific to some nematode lineages and find an unexpected nuclear localization signal conserved in many Dsh orthologs. Our findings raise questions of protein evolution in general and provide clues as to how animals have dealt with the complex intricacies of having a protein, such as Dsh, act as a central messenger hub connected to many different and vitally important pathways. We discuss our findings in the context of functional specialization and bring many testable hypotheses to light.
盘绕蛋白（Dsh 或 Dvl）是一种重要的信号蛋白，在 Wnt 信号转导中发挥关键作用，并为几条发育途径传递细胞信息。Dsh 在后生动物中高度保守，并在大多数两侧对称动物的谱系中扩展为一个多基因家族，包括脊椎动物、扁形动物和线虫。这些同源物在功能上有很大的重叠，但功能特化的证据仍在不断增加。我们对动物中的 Dsh 进行了比较分析，以探索蛋白质结构，并确定保守和分化的特征，这些特征可以为功能特化提供深入了解，重点是无脊椎动物，特别是线虫。我们发现 Dsh 的进化具有动态性，特别是在线虫中，不同分类单元的同源物数量从一个到三个不等。我们鉴定了一个新的结构域，它存在于一些线虫谱系中，并发现了一个令人惊讶的核定位信号，在许多 Dsh 同源物中保守。我们的研究结果提出了蛋白质进化的一般问题，并为动物如何应对将一种蛋白质（如 Dsh）作为连接许多不同且至关重要途径的中央信使枢纽的复杂情况提供了线索。我们在功能特化的背景下讨论了我们的发现，并提出了许多可检验的假设。
