Abair Tristin D, Sundaramoorthy Munirathinam, Chen Dong, Heino Jyrki, Ivaska Johanna, Hudson Billy G, Sanders Charles R, Pozzi Ambra, Zent Roy
Department of Medicine, Division of Nephrology, Vanderbilt University, Nashville, TN 37232, USA.
Exp Cell Res. 2008 Nov 15;314(19):3593-604. doi: 10.1016/j.yexcr.2008.08.014. Epub 2008 Sep 3.
The collagen-binding integrins alpha1beta1 and alpha2beta1 have profoundly different functions, yet they are often co-expressed in epithelial cells. When both integrins are expressed in the same cell, it has been suggested that alpha1beta1 negatively regulates integrin alpha2beta1-dependent functions. In this study we utilized murine ureteric bud (UB) epithelial cells, which express no functionally detectable levels of endogenous integrins alpha1beta1 and alpha2beta1, to determine the mechanism whereby this regulation occurs. We demonstrate that UB cells expressing integrin alpha2beta1, but not alpha1beta1 adhere, migrate and proliferate on collagen I as well as form cellular cords in 3D collagen I gels. Substitution of the transmembrane domain of the integrin alpha2 subunit with that of alpha1 results in decreased cell adhesion, migration and cord formation. In contrast, substitution of the integrin alpha2 cytoplasmic tail with that of alpha1, decreases cell migration and cord formation, but increases proliferation. When integrin alpha1 and alpha2 subunits are co-expressed in UB cells, the alpha1 subunit negatively regulates integrin alpha2beta1-dependent cord formation, adhesion and migration and this inhibition requires expression of both alpha1 and alpha2 tails. Thus, we provide evidence that the transmembrane and cytoplasmic domains of the alpha2 integrin subunit, as well as the alpha1 integrin subunit, regulate integrin alpha2beta1 cell function.
胶原结合整合素α1β1和α2β1具有截然不同的功能，但它们常常在上皮细胞中共表达。当这两种整合素在同一细胞中表达时，有人提出α1β1会负向调节整合素α2β1依赖的功能。在本研究中，我们利用小鼠输尿管芽（UB）上皮细胞，其不表达功能上可检测到的内源性整合素α1β1和α2β1，来确定这种调节发生的机制。我们证明，表达整合素α2β1而非α1β1的UB细胞在I型胶原上黏附、迁移和增殖，并且在三维I型胶原凝胶中形成细胞索。用α1的跨膜结构域替换整合素α2亚基的跨膜结构域会导致细胞黏附、迁移和索形成减少。相反，用α1的整合素α2胞质尾替换，会减少细胞迁移和索形成，但会增加增殖。当整合素α1和α2亚基在UB细胞中共表达时，α1亚基负向调节整合素α2β1依赖的索形成、黏附和迁移，并且这种抑制需要α1和α2尾的表达。因此，我们提供证据表明，α2整合素亚基以及α1整合素亚基的跨膜和胞质结构域调节整合素α2β1的细胞功能。
