TspanC8 tetraspanins differentially regulate the cleavage of ADAM10 substrates, Notch activation and ADAM10 membrane compartmentalization.
TspanC8 tetraspanins differentially regulate the cleavage of ADAM10 substrates, Notch activation and ADAM10 membrane compartmentalization.
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TSPANC8四跨果素差异调节ADAM10底物，Notch活化和ADAM10膜隔室的裂解。
DOI：
10.1007/s00018-015-2111-z
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发表时间：
2016-05
期刊：
影响因子：
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通讯作者：
Rubinstein E
中科院分区：
文献类型：
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作者：
Jouannet S;Saint-Pol J;Fernandez L;Nguyen V;Charrin S;Boucheix C;Brou C;Milhiet PE;Rubinstein E
金属蛋白酶ADAM 10介导各种细胞膜蛋白的胞外域脱落，包括APP、淀粉样肽Aβ的前体和配体结合后的Notch受体。ADAM 10与进化上保守的四跨膜蛋白亚组的成员（称为TspanC 8）相关，该亚组调节其从内质网的退出。在这里，我们表明，这些TspanC 8（Tspan 5，Tspan 14，Tspan 15和Tspan 33），积极调节ADAM 10的表面表达水平差异影响ADAM 10依赖的Notch激活和切割的几个ADAM 10底物，包括APP，N-钙粘蛋白和CD 44。蔗糖梯度分离，单分子跟踪和定量质谱分析的剧目的分子共免疫沉淀Tspan 5，Tspan 15和ADAM 10表明，这两个tetraspanins差异调节ADAM 10膜区室化。这些数据代表了一个独特的例子，其中几个四跨膜蛋白差异调节功能的一个共同的合作伙伴蛋白通过一个独特的膜区室化。本文的在线版本（doi：10.1007/s 00018 -015-2111-z）包含补充材料，可供授权用户使用。
The metalloprotease ADAM10 mediates the shedding of the ectodomain of various cell membrane proteins, including APP, the precursor of the amyloid peptide Aβ, and Notch receptors following ligand binding. ADAM10 associates with the members of an evolutionary conserved subgroup of tetraspanins, referred to as TspanC8, which regulate its exit from the endoplasmic reticulum. Here we show that 4 of these TspanC8 (Tspan5, Tspan14, Tspan15 and Tspan33) which positively regulate ADAM10 surface expression levels differentially impact ADAM10-dependent Notch activation and the cleavage of several ADAM10 substrates, including APP, N-cadherin and CD44. Sucrose gradient fractionation, single molecule tracking and quantitative mass-spectrometry analysis of the repertoire of molecules co-immunoprecipitated with Tspan5, Tspan15 and ADAM10 show that these two tetraspanins differentially regulate ADAM10 membrane compartmentalization. These data represent a unique example where several tetraspanins differentially regulate the function of a common partner protein through a distinct membrane compartmentalization. The online version of this article (doi:10.1007/s00018-015-2111-z) contains supplementary material, which is available to authorized users.