Assembly of urothelial plaques: Tetraspanin function in membrane protein trafficking
Assembly of urothelial plaques: Tetraspanin function in membrane protein trafficking
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DOI：
10.1091/mbc.e05-02-0136
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发表时间：
2005-09-01
影响因子：
3.3
通讯作者：
Sun, TT
中科院分区：
文献类型：
--
作者：
Hu, CCA;Liang, FX;Sun, TT
哺乳动物尿道上皮的顶面覆盖着16-nm的蛋白颗粒，这些颗粒以六边形排列，形成不对称单位膜（AUM）的2D晶体，这些晶体有助于膀胱的显著渗透屏障功能。我们以前已经表明，牛AUM含有四种主要的整合膜蛋白，即，尿斑蛋白Ia、Ib、II和IIIa，并且UPIa和Ib（均为四跨膜蛋白）分别与UPII和IIIa形成异二聚体。使用一组识别不同构象状态的uroplakins的抗体，我们证明了UPII的原序列的UPIA依赖性，弗林蛋白酶介导的切割导致全球成熟UPII的构象变化，UPIB也诱导其合作伙伴UPIIIa的构象变化。我们进一步证明四跨膜蛋白CD 9、CD 81和CD 82可以稳定它们的伴侣蛋白CD 4。这些结果表明，四跨膜蛋白uroplakins，和其他一些四跨膜蛋白，可以诱导构象变化，导致ER退出，稳定，和细胞表面表达的相关，单跨膜结构域的伴侣蛋白，因此可以作为“成熟促进剂”。“我们提出了一个AUM组装模型，其中由尿斑蛋白相互作用，分化依赖性糖基化和UPII前序列的去除诱导的膜蛋白的构象变化在调节尿斑蛋白组装形成AUM中发挥作用。
The apical surface of mammalian urothelium is covered by 16-nm protein particles packed hexagonally to form 2D crystals of asymmetric unit membranes (AUM) that contribute to the remarkable permeability barrier function of the urinary bladder. We have shown previously that bovine AUMs contain four major integral membrane proteins, i.e., uroplakins Ia, Ib, II, and IIIa, and that UPIa and Ib (both tetraspanins) form heterodimers with UPII and IIIa, respectively. Using a panel of antibodies recognizing different conformational states of uroplakins, we demonstrate that the UPIa-dependent, furin-mediated cleavage of the prosequence of UPII leads to global conformational changes in mature UPII and that UPIb also induces conformational changes in its partner UPIIIa. We further demonstrate that tetraspanins CD9, CD81, and CD82 can stabilize their partner protein CD4. These results indicate that tetraspanin uroplakins, and some other tetraspanin proteins, can induce conformational changes leading to the ER-exit, stabilization, and cell surface expression of their associated, single-transmembrane-domained partner proteins and thus can function as "maturation-facilitators." We propose a model of AUM assembly in which conformational changes in integral membrane proteins induced by uroplakin interactions, differentiation-dependent glycosylation, and the removal of the prosequence of UPII play roles in regulating the assembly of uroplakins to form AUM.