The cell-adhesion G protein-coupled receptor BAI3 is a high-affinity receptor for C1q-like proteins
The cell-adhesion G protein-coupled receptor BAI3 is a high-affinity receptor for C1q-like proteins
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DOI：
10.1073/pnas.1019577108
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发表时间：
2011-02-08
影响因子：
11.1
通讯作者：
Suedhof, Thomas C.
中科院分区：
文献类型：
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作者：
Bolliger, Marc F.;Martinelli, David C.;Suedhof, Thomas C.
类C1q基因(C1ql1-C1ql4)编码小的、分泌的蛋白质，这些蛋白质在大脑中以不同的模式表达，但其受体和功能尚不清楚。相比之下，BAI3蛋白是G蛋白偶联受体中细胞黏附类的一员，这种受体在大脑中高水平表达，但其配体迄今未被识别。利用生化方法，我们证明了这四种C1ql蛋白都与BAI3的胞外凝血酶原蛋白重复结构域高亲和力地结合，并且这种结合是由C1ql蛋白的球状C1q结构域介导的。此外，我们证明，在培养的神经元中加入亚微摩尔浓度的C1q1蛋白会导致突触密度显著下降，这种下降可以通过同时添加与C1q1蛋白结合的BAI3的凝血酶敏感蛋白重复片段来防止。我们的数据表明，C1ql蛋白是分泌的信号分子，与BAI3结合，至少部分地调节突触的形成和/或维持。
C1q-like genes (C1ql1-C1ql4) encode small, secreted proteins that are expressed in differential patterns in the brain but whose receptors and functions remain unknown. BAI3 protein, in contrast, is a member of the cell-adhesion class of G protein-coupled receptors that are expressed at high levels in the brain but whose ligands have thus far escaped identification. Using a biochemical approach, we show that all four C1ql proteins bind to the extracellular thrombospondin-repeat domain of BAI3 with high affinity, and that this binding is mediated by the globular C1q domains of the C1ql proteins. Moreover, we demonstrate that addition of submicromolar concentrations of C1ql proteins to cultured neurons causes a significant decrease in synapse density, and that this decrease was prevented by simultaneous addition of the thrombospondin-repeat fragment of BAI3, which binds to C1ql proteins. Our data suggest that C1ql proteins are secreted signaling molecules that bind to BAI3 and act, at least in part, to regulate synapse formation and/or maintenance.