Genomic organization and expression profile of the mucin-associated surface protein (masp) family of the human pathogen Trypanosoma cruzi

Genomic organization and expression profile of the mucin-associated surface protein (masp) family of the human pathogen Trypanosoma cruzi
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DOI:
10.1093/nar/gkp172
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发表时间:
2009-06-01
影响因子:
14.9
通讯作者:
El-Sayed, Najib M.
El-Sayed, Najib M.
中科院分区:
生物学2区
文献类型:
--
作者:
Bartholomeu, Daniella C.;Cerqueira, Gustavo C.;El-Sayed, Najib M.

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最近在人类病原体克氏锥虫(锥虫病的病原体)中发现了一个新的大型多基因家族,相当于寄生虫二倍体基因组的6%。预测的基因产物,粘蛋白相关表面蛋白(MASPs),其特征在于高度保守的N-和C-末端结构域和一个惊人的可变和重复的中心区域。我们在这里报告的masp基因的基因组组织和表达谱的分析。Masp不是随机分布在整个基因组中,而是与编码粘蛋白和其他表面蛋白家族的基因簇在一起。Masp转录物大小不同,优先在锥鞭毛体阶段表达,并含有高度保守的5'和3'非翻译区。锥鞭毛体cDNA文库的序列分析揭示了多个masp变体的表达,其偏向于特定的masp亚组。使用针对MASP肽产生的抗体的免疫荧光测定揭示了特定MASP在细胞膜上的表达限于寄生虫群体的亚群。磷脂酰肌醇特异性磷脂酶C(PI-PLC)处理的寄生虫的蛋白质印迹表明MASP可以是GPI锚定的并脱落到培养基培养物中,从而有助于暴露于宿主免疫系统的寄生虫多肽的大库。
A novel large multigene family was recently identified in the human pathogen Trypanosoma cruzi, causative agent of Chagas disease, and corresponds to similar to 6% of the parasite diploid genome. The predicted gene products, mucin-associated surface proteins (MASPs), are characterized by highly conserved N- and C-terminal domains and a strikingly variable and repetitive central region. We report here an analysis of the genomic organization and expression profile of masp genes. Masps are not randomly distributed throughout the genome but instead are clustered with genes encoding mucin and other surface protein families. Masp transcripts vary in size, are preferentially expressed during the trypomastigote stage and contain highly conserved 5' and 3' untranslated regions. A sequence analysis of a trypomastigote cDNA library reveals the expression of multiple masp variants with a bias towards a particular masp subgroup. Immunofluorescence assays using antibodies generated against a MASP peptide reveals that the expression of particular MASPs at the cell membrane is limited to subsets of the parasite population. Western blots of phosphatidylinositol-specific phospholipase C (PI-PLC)-treated parasites suggest that MASP may be GPI-anchored and shed into the medium culture, thus contributing to the large repertoire of parasite polypeptides that are exposed to the host immune system.