CSMD1 is a novel multiple domain complement-regulatory protein highly expressed in the central nervous system and epithelial tissues
CSMD1 is a novel multiple domain complement-regulatory protein highly expressed in the central nervous system and epithelial tissues
复制标题
DOI：
10.4049/jimmunol.176.7.4419
复制
发表时间：
2006-04-01
影响因子：
4.4
通讯作者：
Holers, V. Michael
中科院分区：
文献类型：
--
作者：
Kraus, Damian M.;Elliott, Gary S.;Holers, V. Michael
在这项研究中，我们描述了一种新的多结构域补体调节蛋白的鉴定和体外功能活性的基础上发现其同源性短的共识重复序列（SCR）的补体激活（RCA）基因家族的调节蛋白。大鼠cDNA编码预测的388-kDa蛋白质，由14个N-末端CUB结构域组成，这些结构域通过SCR彼此分开，随后是15个串联SCR结构域、跨膜结构域和短胞质尾。这种蛋白质是功能未知的人类蛋白质的同源物，称为CUB和寿司多结构域1（CSMD 1）蛋白。一个克隆策略，包括两个C-末端CUB-SCR结构域和12个串联的SCR重复序列被用来产生可溶性大鼠CSMD 1蛋白。该蛋白以与大鼠Crry相当的方式阻断经典补体途径活化，但不阻断旁路途径活化。通过原位杂交和免疫标记神经元的CSMD 1 mRNA表达的分析表明，合成的主要位点是发育中的CNS和上皮组织。特别重要的是CSMD 1在神经生长锥中的富集，神经生长锥是生长神经元的变形虫前缘。这些结果表明，CSMD 1可能是发育中的CNS中补体激活和炎症的重要调节剂，并且它也可能在生长锥功能的背景下发挥作用。
In this study, we describe the identification and in vitro functional activity of a novel multiple domain complement regulatory protein discovered based on its homology to short consensus repeat (SCR)-containing proteins of the regulators of complement activation (RCA) gene family. The rat cDNA encodes a predicted 388-kDa protein consisting of 14 N-terminal CUB domains that are separated from each other by a SCR followed by 15 tandem SCR domains, a transmembrane domain, and a short cytoplasmic tail. This protein is the homolog of the human protein of unknown function called the CUB and sushi multiple domains 1 (CSMD1) protein. A cloning strategy that incorporates the two C-terminal CUB-SCR domains and 12 of the tandem SCR repeats was used to produce a soluble rat CSMD1 protein. This protein blocked classical complement pathway activation in a comparable fashion with rat Crry but did not block alternative pathway activation. Analysis of CSMD1 mRNA expression by in situ hybridization and immunolabeling of neurons indicates that the primary sites of synthesis are the developing CNS and epithelial tissues. Of particular significance is the enrichment of CSMD1 in the nerve growth, cone, the amoeboid-leading edge of the growing neuron. These results suggest that CSMD1 may be an important regulator of complement activation and inflammation in the developing CNS, and that it may also play a role in the context of growth cone function.