The Members of the Highly DiverseCrassostrea gigasIntegrin Family Cooperate for the Generation of Various Immune Responses

Studies on invertebrate immune receptors can provide insights into characteristics specific to innate immune system. Here, eight alpha and three beta integrins are identified from an invertebrate, the Pacific oysterCrassostrea gigas, and their possible immune functions are studied. Oyster alpha/beta integrins exhibit a higher degree of sequence and structural variability than the members fromHomo sapiensandDrosophila melanogaster. The analysis reveals that oyster RGD- and laminin-binding receptor homologs are present in the phylogenetic tree of alpha integrins, but the other six oyster alpha integrins mainly form a species-specific branch; meanwhile, oyster beta integrins are clustered with insect beta integrins but distinct from a member from the molluskBiomphalaria glabrata. Although phylogenetically lacking the important alpha integrin branches of LDV-binding, PS3-type, and alpha I-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 beta integrins are arranged in the core to mediate complex immune responses, unlike the counterparts in humans that mainly depend on alpha I-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 invertebrateC. gigasand sheds light on the characteristics specific to the innate immune system in the integrin family.