As a member of natural resistance-associated macrophage protein (Nramp) family, Nramp2 conservatively exists in the cell membrane across species and is essential for normal iron homeostasis in an H⁺-dependent manner. Withholding available iron represents an important host defense strategy. However, the function of Nramp2 in response to invading pathogens is largely unknown in invertebrates. In this study, a unique echinoderm Nramp2 was identified from sea cucumber Apostichopus japonicus (designated as AjNramp2). The cDNA sequence of AjNramp2 was 2360 bp, with a putative open reading frame of 1713 bp, encoding a typical Nramp domain containing protein with 570 amino acid residues. Structural analysis revealed that AjNramp2 consisted of highly conserved helix regions similar with the human Nramp2. Spatial expression analysis revealed that AjNramp2 was ubiquitously expressed in all examined tissues, with the highest level found in the intestine. Immunohistochemistry assay showed that AjNramp2 was mainly located in the cellular membrane in coelomocytes. Vibrio splendidus challenge and lipopolysaccharide (LPS) stimulation could significantly promote the expression of AjNramp2, which was consistent with the cellular iron level in coelomocytes. Moreover, when the expression of AjNramp2 was knocked down by siRNA-AjNramp2, the cellular iron level was coordinately decreased in coelomocytes under LPS stimulation. Taken together, results indicated that AjNramp2 serves as an iron transport receptor to withhold available iron and may contribute to the nutritional immunity defense system of sea cucumber.

作为天然抗性相关巨噬细胞蛋白 (Nramp) 家族的成员，Nramp2 保守地存在于跨物种的细胞膜中，并且以 H ⁺依赖性方式对正常的铁稳态至关重要。扣留可用的铁代表了一种重要的宿主防御策略。然而，Nramp2 响应入侵病原体的功能在无脊椎动物中很大程度上是未知的。在这项研究中，从海参刺参中鉴定出一种独特的棘皮动物 Nramp2（指定为 AjNramp2）。AjNramp2 的 cDNA 序列为 2360 bp，推定的开放阅读框为 1713 bp，编码一个典型的含有 570 个氨基酸残基的 Nramp 结构域蛋白。结构分析表明，AjNramp2 由与人类 Nramp2 相似的高度保守的螺旋区域组成。空间表达分析显示 AjNramp2 在所有检查的组织中普遍表达，在肠道中发现的水平最高。免疫组化分析显示AjNramp2主要位于体腔细胞的细胞膜上。灿烂弧菌挑战和脂多糖（LPS）刺激可显着促进AjNramp2的表达，这与体腔细胞中的细胞铁水平一致。此外，当 AjNramp2 的表达被 siRNA-AjNramp2 敲低时，LPS 刺激下体腔细胞中的细胞铁水平协同降低。综上所述，结果表明 AjNramp2 作为铁转运受体来抑制可用铁，并可能有助于海参的营养免疫防御系统。