Sterk Lotus M T, Geuijen Cecile A W, van den Berg José G, Claessen Nike, Weening Jan J, Sonnenberg Arnoud
Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
J Cell Sci. 2002 Mar 15;115(Pt 6):1161-73. doi: 10.1242/jcs.115.6.1161.
CD151 is a cell surface protein that belongs to the tetraspanin superfamily. It forms complexes with the laminin-binding integrins alpha3beta1, alpha6beta1 and alpha6beta4 and is codistributed with these integrins in many tissues at sites of cell-matrix interactions. In this study we show that CD151 can also form stable complexes with the laminin-binding integrin alpha7beta1. The strength of this interaction is comparable to that between CD151 and alpha3beta1. Complexes of alpha3beta1, alpha6beta1 and alpha7beta1 with CD151 are equally well formed with all splice variants of the alpha3, alpha6 and alpha7 subunits, and complex formation is not affected by mutations that prevent the cleavage of the integrin alpha6 subunit. Like the expression of alpha3beta1 and alpha6beta1, expression of alpha7beta1 in K562 cells results in increased levels of CD151 at its surface. Two non-integrin laminin receptors, dystroglycan and the polypeptide on which the Lutheran blood group antigens are expressed, are also often colocalized with CD151, but no association with CD151-alpha3beta1 complexes was found with biochemical analysis. The anti-CD151 antibody TS151R detects an epitope at a site at which CD151 interacts with integrins, and therefore it cannot react with CD151 when it is bound to an integrin. Comparison of the straining patterns produced by TS151R with that by of an anti-CD151 antibody recognizing an epitope outside the binding site (P48) revealed that most tissues expressing one or more laminin-binding integrins reacted with P48 but not with TS151R. However, smooth muscle cells that express alpha7beta1 and renal tubular epithelial cells that express alpha6beta1 were stained equally well by TS151R and P48. These results suggest that the interactions between CD151 and laminin-binding integrins are subject to cell-type-specific regulation.
CD151是一种细胞表面蛋白,属于四跨膜蛋白超家族。它与层粘连蛋白结合整合素α3β1、α6β1和α6β4形成复合物,并在细胞-基质相互作用位点与这些整合素在许多组织中共分布。在本研究中,我们表明CD151还可与层粘连蛋白结合整合素α7β1形成稳定复合物。这种相互作用的强度与CD151和α3β1之间的强度相当。α3β1、α6β1和α7β1与CD151的复合物与α3、α6和α7亚基的所有剪接变体形成得同样好,并且复合物的形成不受阻止整合素α6亚基切割的突变的影响。与α3β1和α6β1的表达一样,K562细胞中α7β1的表达导致其表面CD151水平升高。两种非整合素层粘连蛋白受体,肌营养不良聚糖和表达路德血型抗原的多肽,也经常与CD151共定位,但生化分析未发现它们与CD151-α3β1复合物有关联。抗CD151抗体TS151R在CD151与整合素相互作用的位点检测到一个表位,因此当CD151与整合素结合时它不能与CD151反应。将TS151R产生的染色模式与识别结合位点之外表位(P48)的抗CD151抗体产生的染色模式进行比较,发现大多数表达一种或多种层粘连蛋白结合整合素的组织与P48反应,但不与TS151R反应。然而,表达α7β1的平滑肌细胞和表达α6β1的肾小管上皮细胞被TS151R和P48染色的效果相同。这些结果表明CD151与层粘连蛋白结合整合素之间的相互作用受到细胞类型特异性调节。