Apical Secretory Glycoprotein Complex Contributes to Cell Attachment and Entry by Cryptosporidium parvum.
Apical Secretory Glycoprotein Complex Contributes to Cell Attachment and Entry by Cryptosporidium parvum.
复制标题
作者：
微小隐孢子虫是一种肠道病原体，它侵入肠上皮细胞，在那里它驻留在顶端表面的一个独特的细胞外位置。与相关的顶复门寄生虫相比，C. parvum知之甚少。流线型的C. parvum基因组包含许多粘蛋白样糖蛋白，其中几种先前已显示介导细胞附着，尽管大多数尚未研究。在这里，我们确定了单克隆抗体（MAb）1A 5，它染色的顶端的子孢子和成熟裂殖子识别的抗原。用MAb 1A 5免疫沉淀，然后质谱鉴定了一种异源二聚体，其由与C. parvum和相关物种。由MAb 1A 5识别的旁系同源糖蛋白异源二聚体作为在寄生虫表面上显示的复合物，并且它们还与表明它们含有粘蛋白样O-连接寡糖的凝集素相互作用。尽管编码其中一种旁系同源物的基因很容易被CRISPR/Cas9基因编辑破坏，但它的伴侣（包含与GP 900相关的粘蛋白样结构域）难以删除。结合MAb 1A 5的能力，部分中和宿主细胞附着的子孢子，这些研究结果定义了一个新的家族的分泌糖蛋白，参与细胞入侵隐孢子虫属。
Cryptosporidium parvum is an enteric pathogen that invades epithelial cells in the intestine, where it resides at the apical surface in a unique epicellular location. Compared with those of related apicomplexan parasites, the processes of host cell attachment and invasion by C. parvum are poorly understood. The streamlined C. parvum genome contains numerous mucin-like glycoproteins, several of which have previously been shown to mediate cell attachment, although the majority are unstudied. Here, we identified the antigens recognized by monoclonal antibody (MAb) 1A5, which stains the apical end of sporozoites and mature merozoites. Immunoprecipitation with MAb 1A5 followed by mass spectrometry identified a heterodimer comprised of paralogous proteins which are related to additional orthologs in the genome of C. parvum and related species. Paralogous glycoproteins recognized by MAb 1A5 heterodimerize as a complex displayed on the parasite surface, and they also interact with lectins that suggest that they contain mucin-like, O-linked oligosaccharides. Although the gene encoding one of the paralogs was readily disrupted by CRISPR/Cas9 gene editing, its partner, which contains a mucin-like domain related to GP900, was refractory to deletion. Combined with the ability of MAb 1A5 to partially neutralize host cell attachment by sporozoites, these findings define a new family of secretory glycoproteins that participate in cell invasion by Cryptosporidium spp.
登录
查看更多内容
影响因子：
168.9
作者：
Kotloff, Karen L.;Nataro, James P.;Levine, Myron M.
通讯作者：
Levine, Myron M.
影响因子：
14.9
作者：
Dereeper A;Guignon V;Blanc G;Audic S;Buffet S;Chevenet F;Dufayard JF;Guindon S;Lefort V;Lescot M;Claverie JM;Gascuel O
通讯作者：
Gascuel O
DOI：
10.1111/j.1550-7408.1986.tb05567.x
发表时间：
1986-02-01
期刊：
JOURNAL OF PROTOZOOLOGY
影响因子：
--
作者：
CURRENT, WL;REESE, NC
通讯作者：
REESE, NC
影响因子：
3.4
作者：
Sanderson, Sanya J.;Xia, Dong;Wastling, Jonathan M.
通讯作者：
Wastling, Jonathan M.
影响因子：
3.1
作者：
Cevallos, AM;Zhang, XP;Ward, HD
通讯作者：
Ward, HD