Emergence of a Thrombospondin Superfamily at the Origin of Metazoans
Emergence of a Thrombospondin Superfamily at the Origin of Metazoans
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DOI：
10.1093/molbev/msz060
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发表时间：
2019-03
影响因子：
10.7
通讯作者：
D. Shoemark;B. Ziegler;Hiroshi Watanabe;Jennifer Strompen;R. Tucker;S. Özbek;J. Adams
中科院分区：
文献类型：
--
作者：
D. Shoemark;B. Ziegler;Hiroshi Watanabe;Jennifer Strompen;R. Tucker;S. Özbek;J. Adams
摘要细胞外基质（ECM）被认为是后生动物多细胞性进化的核心，然而，ECM蛋白在非两侧体动物中的组成仍不清楚。血小板反应蛋白（TSPs）是一个非常保守的蛋白家族，主要研究脊椎动物的基质细胞功能。通过利用TSP的高度保守的C-末端区域的搜索，我们确定了未公开的新的家庭的TSP相关蛋白的后生动物，指定的巨型TSP，寿司TSP，和poriferan-TSP，每个具有独特的系统发育分布。这些蛋白质共享TSP C-末端区域结构域架构，如通过针对已知结构的分子模型的结构域组成和分析所确定的。Mega-TSP是在栉水母中鉴定的唯一形式，通常> 2，700 aa，并且还以N-末端富含亮氨酸的重复序列和中央钙粘蛋白/免疫球蛋白结构域为特征。在刺胞动物中，它有一个明确的ECM，Mega-TSP在整个胚胎发生中表达的Nematostella vectensis，动态内胚层表达的幼虫和初级息肉和广泛的外胚层表达的成年Nematostella vectensis和水螅magnipripata息肉。Hydra Mega-TSP在再生过程中也表达，并且在Hydra中Mega-TSP的siRNA沉默引起头部再生的特异性阻断。基于保守的TSP C-末端区域的分子系统发育分析确定了每个TSP相关组形成不同于典型TSP的分支。我们讨论了新定义的TSP超家族的进化模型的基因复制，辐射，和基因丢失首次亮相在最后的后生动物共同祖先。总之，这些数据为后生动物ECM和组织组织的演变提供了新的见解。
Abstract Extracellular matrix (ECM) is considered central to the evolution of metazoan multicellularity; however, the repertoire of ECM proteins in nonbilaterians remains unclear. Thrombospondins (TSPs) are known to be well conserved from cnidarians to vertebrates, yet to date have been considered a unique family, principally studied for matricellular functions in vertebrates. Through searches utilizing the highly conserved C-terminal region of TSPs, we identify undisclosed new families of TSP-related proteins in metazoans, designated mega-TSP, sushi-TSP, and poriferan-TSP, each with a distinctive phylogenetic distribution. These proteins share the TSP C-terminal region domain architecture, as determined by domain composition and analysis of molecular models against known structures. Mega-TSPs, the only form identified in ctenophores, are typically >2,700 aa and are also characterized by N-terminal leucine-rich repeats and central cadherin/immunoglobulin domains. In cnidarians, which have a well-defined ECM, Mega-TSP was expressed throughout embryogenesis in Nematostella vectensis, with dynamic endodermal expression in larvae and primary polyps and widespread ectodermal expression in adult Nematostella vectensis and Hydra magnipapillata polyps. Hydra Mega-TSP was also expressed during regeneration and siRNA-silencing of Mega-TSP in Hydra caused specific blockade of head regeneration. Molecular phylogenetic analyses based on the conserved TSP C-terminal region identified each of the TSP-related groups to form clades distinct from the canonical TSPs. We discuss models for the evolution of the newly defined TSP superfamily by gene duplications, radiation, and gene losses from a debut in the last metazoan common ancestor. Together, the data provide new insight into the evolution of ECM and tissue organization in metazoans.