Functional analysis of four tetraspans, CD9, CD53, CD81, and CD82, suggests a common role in costimulation, cell adhesion, and migration:: Only CD9 upregulates HB-EGF activity
Functional analysis of four tetraspans, CD9, CD53, CD81, and CD82, suggests a common role in costimulation, cell adhesion, and migration:: Only CD9 upregulates HB-EGF activity
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DOI：
10.1006/cimm.1997.1223
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发表时间：
1997-12-15
影响因子：
4.3
通讯作者：
Rubinstein, E
中科院分区：
文献类型：
--
作者：
Lagaudrière-Gesbert, C;Le Naour, F;Rubinstein, E
Tetraspan超家族的分子参与了含有其他蛋白质的多分子复合体，如Beta1整合素和MHC抗原。虽然它们的功能尚不清楚，但已被认为在细胞黏附和迁移、信号转导和共刺激中发挥作用。我们在本文中直接比较了CD9、CD53、CD81和CD82四种四聚糖的功能性质。这些分子中的任何一个分子的单抗都能够为CD3介导的T细胞系Jurkat的激活传递共刺激信号。CD82单抗是触发这种效应的最有效的单抗。此外，CD9、CD81和CD82的结合可诱导巨核细胞系HEL的同型聚集，并抑制该细胞系的迁移。用CD9和CD81单抗在Preb细胞株NALM-6中也得到了类似的结果。CD81mAb5A6的作用最强。因此，对相同的细胞系产生类似作用的单抗可以识别四聚糖。这与四聚糖被包含在大分子复合体中并可能形成四聚糖网络(四聚糖网)是一致的。我们还证明了四聚糖可能在这个网络中保持特定的功能性质。事实上，我们已经证明，当共转染小鼠LM细胞时，人CD9能够像猴子分子一样，上调肝素结合EGF的跨膜前体作为白喉毒素受体的活性。CD81和CD82均无此活性。通过使用嵌合的CD9/CD81分子，我们证明了这种活性需要CD9的后半部分，它包含大的胞外环、第四个跨膜区和最后一个较短的细胞质结构域。(C)1997年学术出版社。
Molecules of the tetraspan superfamily are engaged in multimolecular complexes containing other proteins such as beta1 integrins and MHC antigens. Although their functions are not clear, they have been suggested to play a role in cell adhesion and migration, signal transduction, and costimulation. We have in this paper directly compared the functional properties of four tetraspans, CD9, CD53, CD81, and CD82. mAbs to any of these molecules were able to deliver a costimulatory signal for CD3-mediated activation of the T cell line Jurkat. CD82 mAbs were the most efficient in triggering this effect. Moreover, engagement of CD9, CD81, and CD82 induced the homotypic aggregation of the megakaryocytic cell line HEL, and inhibited the migration of this cell line. Similar results were obtained with the preB cell line NALM-6 using the CD9 and CD81 mAbs. The CD81 mAb 5A6 produced the strongest effects. Therefore, the tetraspans are recognized by mAbs which produce similar effects on the same cell lines. This is consistent with the tetraspans being included in large molecular complexes and possibly forming a tetraspan network (the tetraspan web). We also demonstrate that the tetraspans are likely to keep specific functional properties inside this network. Indeed, we have demonstrated that the human CD9 is able, like the monkey molecule, to upregulate the activity of the transmembrane precursor of heparin-binding EGF as a receptor for the diphtheria toxin when cotransfected in murine LM cells. Neither CD81, nor CD82 had such activity. By using chimeric CD9/CD81 molecules we demonstrate that this activity requires the second half of CD9, which contains the large extracellular loop, the fourth transmembrane region, and the last short cytoplasmic domain. (C) 1997 Academic Press.