Nature:Orai1突变引发免疫缺陷
生物谷报道：免疫细胞抗原刺激通过非特异性钙通透触发Ca2+的内流，从而激发转录因子NFAT来促进机体对病原体的免疫反应。遗传性免疫缺乏症患者细胞缺乏钙库调控性Ca2+内流及CRAC通道。采用SNP和果蝇RNA干扰屏鉴定这些病人的基因缺陷性,发现一个含四个跨膜结构的新蛋白Orai1与该病相关。SCID患者是ORAI1错义突变纯合体，野生型Orai1在SCIDT细胞中的表达可恢复钙库调控性Ca2+内流和CRAC的流通。Orai1是可能是CRAC通道复合体的组成成分或调节物。
原始出处:A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function.
Antigen stimulation of immune cells triggers Ca2+ entry through Ca2+ release-activated Ca2+ (CRAC) channels, promoting the immune response to pathogens by activating the transcription factor NFAT. We have previously shown that cells from patients with one form of hereditary severe combined immune deficiency (SCID) syndrome are defective in store-operated Ca2+ entry and CRAC channel function. Here we identify the genetic defect in these patients, using a combination of two unbiased genome-wide approaches: a modified linkage analysis with single-nucleotide polymorphism arrays, and a Drosophila RNA interference screen designed to identify regulators of store-operated Ca2+ entry and NFAT nuclear import. Both approaches converged on a novel protein that we call Orai1, which contains four putative transmembrane segments. The SCID patients are homozygous for a single missense mutation in ORAI1, and expression of wild-type Orai1 in SCID T cells restores store-operated Ca2+ influx and the CRAC current (ICRAC). We propose that Orai1 is an essential component or regulator of the CRAC channel complex.
友情连接:Orai1突变引发免疫缺陷
