The Key Laboratory of Zoological Systematics and Application, College of Life Sciences, Hebei University, Baoding, 071002, China.
Hebei Basic Science Center for Biotic Interaction, Hebei University, Baoding, 071002, China.
BMC Biol. 2024 Oct 23;22(1):242. doi: 10.1186/s12915-024-02042-5.
Single-domain von Willebrand factor type C (SVWC) constitute a protein family predominantly identified in arthropods, characterized by a SVWC domain and involved in diverse physiological processes such as host defense, stress resistance, and nutrient metabolism. Nevertheless, the physiological mechanisms underlying these functions remain inadequately comprehended.
A massive expansion of the SVWC gene family in Musca domestica (MdSVWC) was discovered, with a count of 35. MdSVWC1 was selected as the representative of the SVWC family for functional analysis, which led to the identification of the immune function of MdSVWC1 as a novel pattern recognition receptor. MdSVWC1 is highly expressed in both the fat body and intestines and displays acute induction upon bacterial infection. Recombinant MdSVWC1 binds to surfaces of both bacteria and yeast through the recognition of multiple pathogen-associated molecular patterns and exhibits Ca-dependent agglutination activity. MdSVWC1 mutant flies exhibited elevated mortality and hindered bacterial elimination following bacterial infection as a result of reduced hemocyte phagocytic capability and weakened expression of antimicrobial peptide (AMP) genes. In contrast, administration of recombinant MdSVWC1 provided protection to flies from bacterial challenges by promoting phagocytosis and AMP genes expression, thereby preventing bacterial colonization. MdSPN16, a serine protease inhibitor, was identified as a target protein of MdSVWC1. It was postulated that the interaction of MdSVWC1 with MdSPN16 would result in the activation of an extracellular proteolytic cascade, which would then initiate the Toll signaling pathway and facilitate the expression of AMP genes.
MdSVWC1 displays activity as a soluble pattern recognition receptor that regulates cellular and humoral immunity by recognizing microbial components and facilitating host defense.
单域血管性血友病因子 C 型（SVWC）构成了一个主要在节肢动物中发现的蛋白质家族，其特征是具有 SVWC 结构域，并参与多种生理过程，如宿主防御、应激抵抗和营养代谢。然而，这些功能的生理机制尚未得到充分理解。
在家蝇（MdSVWC）中发现了 SVWC 基因家族的大规模扩张，共有 35 个成员。选择 MdSVWC1 作为 SVWC 家族的代表进行功能分析，结果表明 MdSVWC1 是一种新的模式识别受体，具有免疫功能。MdSVWC1 在脂肪体和肠道中均高度表达，并在细菌感染时表现出急性诱导。重组 MdSVWC1 通过识别多种病原体相关分子模式与细菌和酵母表面结合，并表现出 Ca 依赖性聚集活性。由于吞噬细胞吞噬能力降低和抗菌肽（AMP）基因表达减弱，MdSVWC1 突变果蝇在细菌感染后死亡率升高，细菌清除能力受阻。相比之下，重组 MdSVWC1 的给药可通过促进吞噬作用和 AMP 基因表达来保护果蝇免受细菌的挑战，从而防止细菌定植。MdSPN16，一种丝氨酸蛋白酶抑制剂，被鉴定为 MdSVWC1 的靶蛋白。据推测，MdSVWC1 与 MdSPN16 的相互作用会导致细胞外蛋白水解级联的激活，从而启动 Toll 信号通路并促进 AMP 基因的表达。
MdSVWC1 作为一种可溶性模式识别受体发挥作用，通过识别微生物成分并促进宿主防御来调节细胞和体液免疫。
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