Table_5_The Members of the Highly Diverse Crassostrea gigas Integrin Family Cooperate for the Generation of Various Immune Responses.xls

Studies on invertebrate immune receptors can provide insights into characteristics specific to innate immune system. Here, eight α and three β integrins are identified from an invertebrate, the Pacific oyster Crassostrea gigas, and their possible immune functions are studied. Oyster α/β integrins exhibit a higher degree of sequence and structural variability than the members from Homo sapiens and Drosophila melanogaster. The analysis reveals that oyster RGD- and laminin-binding receptor homologs are present in the phylogenetic tree of α integrins, but the other six oyster α integrins mainly form a species-specific branch; meanwhile, oyster β integrins are clustered with insect β integrins but distinct from a member from the mollusk Biomphalaria glabrata. Although phylogenetically lacking the important α integrin branches of LDV-binding, PS3-type, and αI-containing integrins, oyster integrins can bind to most ECM ligands, including RGDCP, LDVCP, GFOGERCP, and laminin protein in a distinct binding pattern. Besides, oyster integrins are distributed in different hemocyte subpopulations, while only specific integrins are selectively involved in hemocyte phagocytosis, migration, and encapsulation, and some of them participate in more than one immune response in a sophisticated pattern. Especially, oyster β integrins are arranged in the core to mediate complex immune responses, unlike the counterparts in humans that mainly depend on αI-containing integrins to incite immune reactions. This study represents the first comprehensive attempt to reveal the structural and evolutionary features of the integrin family and their involvement in cellular immune responses in the non-model invertebrate C. gigas and sheds light on the characteristics specific to the innate immune system in the integrin family.

针对无脊椎动物免疫受体的研究，可为揭示先天免疫系统的特有特征提供重要参考。本研究从无脊椎动物太平洋牡蛎（Crassostrea gigas）中鉴定出8种α整合素（integrin）与3种β整合素，并对其潜在免疫功能展开系统性探究。研究发现，太平洋牡蛎的α/β整合素在序列与结构变异程度上，显著高于智人（Homo sapiens）与黑腹果蝇（Drosophila melanogaster）的整合素同源蛋白。系统发育分析显示，牡蛎的RGD结合型与层粘连蛋白结合型受体同源物，存在于α整合素的系统发育树中，但其余6种牡蛎α整合素主要形成一个物种特异性分支；与此同时，牡蛎β整合素与昆虫β整合素聚类，却与软体动物光滑双脐螺（Biomphalaria glabrata）的β整合素存在明显差异。尽管在系统发育层面，牡蛎整合素缺失结合LDV的、PS3型以及含αI结构域的重要α整合素分支，但牡蛎整合素仍可通过独特的结合模式，与绝大多数细胞外基质（extracellular matrix, ECM）配体结合，包括RGDCP、LDVCP、GFOGERCP以及层粘连蛋白。此外，牡蛎整合素在不同的血细胞亚群中呈特异性分布，仅特定的整合素会选择性参与血细胞的吞噬作用、迁移与包囊过程，部分整合素还可通过复杂模式参与多种免疫应答。尤为特别的是，牡蛎β整合素作为核心元件介导复杂的免疫应答，这与人类主要依赖含αI结构域的整合素触发免疫反应的机制截然不同。本研究首次全面揭示了非模式无脊椎动物太平洋牡蛎（C. gigas）中整合素家族的结构与进化特征，及其在细胞免疫应答中的作用，为阐明整合素家族先天免疫系统的特有特征提供了关键见解。