Identification of MarvelD3 as a tight junction-associated transmembrane protein of the occludin family.

Identification of MarvelD3 as a tight junction-associated transmembrane protein of the occludin family.
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DOI:
10.1186/1471-2121-10-95
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发表时间:
2009-12-22
期刊:
影响因子:
--
通讯作者:
Matter K
Matter K
中科院分区:
生物3区
文献类型:
--
作者:
Steed E;Rodrigues NT;Balda MS;Matter K

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紧密连接是上皮细胞和内皮细胞的细胞间粘附复合物,并形成细胞旁屏障,根据大小和电荷限制溶质的扩散。紧密连接是由含有胞质蛋白和跨膜蛋白的多蛋白复合物形成的。这些成分是如何一起工作形成功能性紧密连接的,目前还不清楚,需要对连接的分子组成有一个完整的了解。在这里,我们鉴定了紧密连接的一个新的跨膜成分:MarvelD3,一个四跨跨膜蛋白。其预测的跨膜螺旋形成了一个Marvel (MAL和相关的囊泡交通和膜连接蛋白)结构域,这是一个结构基元,最初发现于参与膜附着和融合事件的蛋白质中,如紧密连接蛋白occludin和tricellulin。在哺乳动物中,MarvelD3以两种选择性剪接的同工异构体表达。这两种异构体表现出广泛的组织分布,并由不同类型的上皮细胞和内皮细胞表达。MarvelD3与occludin共同定位在肠和角膜上皮细胞的紧密连接处。Caco-2细胞的RNA干扰实验表明,形成功能性紧密连接不需要正常的MarvelD3表达,但缺失会导致单层细胞的上皮电阻增加。我们的数据表明,MarvelD3是跨膜蛋白紧密连接相关闭塞蛋白家族的第三个成员。与occludin类似,正常表达的MarvelD3对于功能性紧密连接的形成并不是必需的。然而,MarvelD3是上皮细胞旁通透性的决定因素。
Tight junctions are an intercellular adhesion complex of epithelial and endothelial cells, and form a paracellular barrier that restricts the diffusion of solutes on the basis of size and charge. Tight junctions are formed by multiprotein complexes containing cytosolic and transmembrane proteins. How these components work together to form functional tight junctions is still not well understood and will require a complete understanding of the molecular composition of the junction. Here we identify a new transmembrane component of tight junctions: MarvelD3, a four-span transmembrane protein. Its predicted transmembrane helices form a Marvel (MAL and related proteins for vesicle traffic and membrane link) domain, a structural motif originally discovered in proteins involved in membrane apposition and fusion events, such as the tight junction proteins occludin and tricellulin. In mammals, MarvelD3 is expressed as two alternatively spliced isoforms. Both isoforms exhibit a broad tissue distribution and are expressed by different types of epithelial as well as endothelial cells. MarvelD3 co-localises with occludin at tight junctions in intestinal and corneal epithelial cells. RNA interference experiments in Caco-2 cells indicate that normal MarvelD3 expression is not required for the formation of functional tight junctions but depletion results in monolayers with increased transepithelial electrical resistance. Our data indicate that MarvelD3 is a third member of the tight junction-associated occludin family of transmembrane proteins. Similar to occludin, normal expression of MarvelD3 is not essential for the formation of functional tight junctions. However, MarvelD3 functions as a determinant of epithelial paracellular permeability properties.
DOI: 10.1007/s002329900393
发表时间: 1998-07-01
影响因子: 2.4
作者:
Calderón, V;Lázaro, A;Cereijido, M
通讯作者: Cereijido, M
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发表时间: 2009-05-01
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发表时间: 2000-05-02
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影响因子: 11.4
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单个基因产物Claudin -1或-2,在成纤维细胞中重构紧密结合的连接链和新兵。
DOI: 10.1083/jcb.143.2.391
发表时间: 1998-10-19
影响因子: 7.8
作者:
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通讯作者: Tsukita, S