Homotrimeric complexes are the dominant assembly state of native P2X7 subunits

Homotrimeric complexes are the dominant assembly state of native P2X7 subunits
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DOI:
10.1016/j.bbrc.2008.10.042
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发表时间:
2008-12-19
影响因子:
3.1
通讯作者:
Nicke, Annette
Nicke, Annette
中科院分区:
生物学4区
文献类型:
--
作者:
Nicke, Annette

文献摘要

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P2 X受体(P2 XRs)是三聚体ATP门控阳离子通道。已经克隆了七个亚单位。P2 X4和P2 X7亚基显示重叠表达,并且这两种亚基都参与病理生理过程,例如炎性和神经性疼痛。本研究采用亚型特异性抗体结合BN-PAGE直接显示天然组织膜提取物中的P2 XR复合物,并与P2 X4/7 R的特异性抗体结合,对P2 X4/7 R复合物进行了定量分析。结果显示,P2 X7 R和P2 X4 R在许多组织中具有特异性染色。P2 X7复合物的大小与P2 X4复合物明显不同,但同样由三个亚基组成。没有复合物对应于三个以上的亚基可以检测到。此外,未检测到中等大小的复合物或与两种抗体反应的复合物。这些数据表明,P2 X4和P2 X7亚基之间的异聚化不会导致稳定的异聚复合物,或者P2 X4/7异聚体在所研究的组织中不代表显性亚型。(C)2008年爱思唯尔公司All rights reserved.
P2X receptors (P2XRs) are trimeric ATP-gated cation channels. Seven Subunits have been cloned. P2X4 and P2X7 Subunits show overlapping expression and both Subunits are involved in pathophysiological processes such as inflammatory and neuropathic pain. A recent study provides evidence for heteromeric P2X4/7Rs.In this study, subtype-specific antibodies in combination with BN-PAGE are used to directly visualize P2XR complexes solubilized from membrane extracts of native tissues. The results show specific P2X7R and P2X4R staining in many tissues. The P2X7 complex has a clearly different size than the P2X4 complex but is likewise composed of three subunits. No complexes corresponding to more than three subunits could be detected. Also, no complexes of intermediate size or reactive to both antibodies were detected. These data suggest that either heteromerization between P2X4 and P2X7 subunits results not in stable heteromeric complexes or P2X4/7 heteromers do not represent a dominant subtype in the tissues investigated. (C) 2008 Elsevier Inc. All rights reserved.