EXPRESSION CLONING OF DSR-CI, A CLASS-C MACROPHAGE-SPECIFIC SCAVENGER RECEPTOR FROM DROSOPHILA-MELANOGASTER
EXPRESSION CLONING OF DSR-CI, A CLASS-C MACROPHAGE-SPECIFIC SCAVENGER RECEPTOR FROM DROSOPHILA-MELANOGASTER
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DOI：
10.1073/pnas.92.9.4056
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发表时间：
1995-04-25
影响因子：
11.1
通讯作者：
KRIEGER, M
中科院分区：
文献类型：
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作者：
PEARSON, A;LUX, A;KRIEGER, M
哺乳动物A类巨噬细胞特异性清道夫受体（SR-A）对多种多阴离子配体表现出异常广泛的结合特异性。这些受体的特性提示它们可能参与动脉粥样硬化和宿主防御。我们之前在黑腹果蝇胚胎巨噬细胞和果蝇巨噬样Schneider L2细胞系中观察到类似的受体活性。利用表达克隆技术从L2细胞中分离出编码第三类（C类）清道夫受体果蝇SR-CI （dSR-CI）的cDNA。胚胎发育过程中，dSR-CI的表达仅限于巨噬细胞/血细胞。当在哺乳动物细胞中表达时，dSR-CI表现出高亲和力和饱和结合i -125标记的乙酰化低密度脂蛋白，并介导其依赖氯喹（可能是溶酶体）的降解。虽然dSR-CI的广泛多阴离子配体结合特异性与SR-A相似，但它们预测的蛋白序列并不相似。dSR-CI是一种609残基I型完整膜蛋白，包含几个众所周知的序列基序，包括两个补体控制蛋白（CCP）结构域和somatomedin B、MAM和粘蛋白样结构域。巨噬细胞清道夫受体介导了重要的、保守的功能，可能是在宿主防御机制进化早期出现的模式识别受体。对果蝇dSR-CI功能的遗传和生理分析，有助于进一步了解清道夫受体在宿主防御和发育中的作用。
Mammalian class A macrophage-specific scavenger receptors (SR-A) exhibit unusually broad binding specificity for a wide variety of polyanionic ligands. The properties of these receptors suggest that they may be involved in atherosclerosis and host defense. We have previously observed a similar receptor activity in Drosophila melanogaster embryonic macrophages and in the Drosophila macrophagelike Schneider L2 cell line. Expression cloning was used to isolate from L2 cells a cDNA that encodes a third class (class C) of scavenger receptor, Drosophila SR-CI (dSR-CI). dSR-CI expression was restricted to macrophages/hemocytes during embryonic development. When expressed in mammalian cells, dSR-CI exhibited high affinity and saturable binding of I-125-labeled acetylated low density lipoprotein and mediated its chloroquine-dependent, presumably lysosomal, degradation. Although the broad polyanionic ligand-binding specificity of dSR-CI was similar to that of SR-A, their predicted protein sequences are not similar. dSR-CI is a 609-residue type I integral membrane protein containing several well-known sequence motifs, including two complement control protein (CCP) domains and somatomedin B, MAM, and mucin-like domains, Macrophage scavenger receptors apparently mediate important, well-conserved functions and may be pattern-recognition receptors that arose early in the evolution of host-defense mechanisms. Genetic and physiologic analysis of dSR-CI function in Drosophila should provide further insights into the roles played by scavenger receptors in host defense and development.