PDF(Pubmed)
Abstract：
In Caenorhabditis elegans, expanded families of divergent Hedgehog-related and patched-related proteins promote numerous processes ranging from epithelial and sense organ development to pathogen responses to cuticle shedding during the molt cycle. The molecular functions of these proteins have been mysterious since nematodes lack a canonical Hedgehog signaling pathway. Here we show that Hedgehog-related proteins are components of the cuticle and precuticle apical extracellular matrices that coat, shape, and protect external epithelia. Of four Hedgehog-related proteins imaged, two (GRL-2 and GRL-18) stably associated with the cuticles of specific tubes and two (GRL-7 and WRT-10) labeled precuticle substructures such as furrows or alae. We found that wrt-10 mutations disrupt cuticle alae ridges, consistent with a structural role in matrix organization. We hypothesize that most nematode Hedgehog-related proteins are apical extracellular matrix components, a model that could explain many of the reported functions for this family. These results highlight ancient connections between Hedgehog proteins and the extracellular matrix and suggest that any signaling roles of C. elegans Hedgehog-related proteins will be intimately related to their matrix association.
摘要：
在秀丽隐杆线虫中，不同的Hedgehog相关和Patched相关蛋白的扩展家族促进了许多过程，从上皮和感觉器官发育到病原体对蜕皮周期中角质层脱落的反应。由于线虫缺乏典型的Hedgehog信号通路，这些蛋白质的分子功能一直是神秘的。在这里，我们显示Hedgehog相关蛋白是表皮和前表皮顶端细胞外基质的组成部分，形状,并保护外部上皮。在成像的四种刺猬相关蛋白中，两个（GRL-2和GRL-18）与特定管的角质层稳定相关，两个（GRL-7和WRT-10）标记的角质层亚结构，例如沟或沟。我们发现wrt-10突变会破坏角质层脊，与矩阵式组织中的结构作用一致。我们假设大多数线虫Hedgehog相关蛋白是顶端细胞外基质成分，一个可以解释这个家族的许多报告功能的模型。这些结果突出了Hedgehog蛋白与细胞外基质之间的古老联系，并表明秀丽隐杆线虫Hedgehog相关蛋白的任何信号作用都将与其基质缔合密切相关。
