Distinct expression of C1q-like family mRNAs in mouse brain and biochemical characterization of their encoded proteins
Distinct expression of C1q-like family mRNAs in mouse brain and biochemical characterization of their encoded proteins
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DOI：
10.1111/j.1460-9568.2010.07202.x
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发表时间：
2010-05-01
影响因子：
3.4
通讯作者：
Yuzaki, Michisuke
中科院分区：
文献类型：
--
作者：
Iijima, Takatoshi;Miura, Eriko;Yuzaki, Michisuke
C1 q家族的许多成员，包括补体C1 q和脂联素，以及结构相关的肿瘤坏死因子家族被分泌，并在细胞间信号传导中发挥关键作用。其中，Cbln（precerebellin）和C1 q样（C1 ql）亚家族在中枢神经系统中高度且主要表达。尽管Cbln亚家族作为小脑中突触完整性的重要跨神经元调节因子，但C1 ql亚家族（C1 ql 1-C1 ql 4）的功能仍未被探索。在这里，我们研究了C1 ql亚家族的基因表达在成年和发育中的小鼠大脑的逆转录-聚合酶链反应和高分辨率原位杂交。在成年脑中，C1 ql 1-C1 ql 3 mRNA主要表达于神经元中，但在成年脑中的胶质样结构中观察到弱表达。C1 ql 1 mRNA主要表达在下橄榄，而C1 ql 2和C1 ql 3 mRNA强烈共表达在齿状回。虽然C1 ql 1和C1 ql 3 mRNA的检测早在胚胎13天，C1 ql 2 mRNA的观察在胚胎后期。C1 ql 1 mRNA在小脑外颗粒层也有短暂表达。在异源细胞中的生物化学表征显示，所有的C1 ql亚家族蛋白被分泌，并且它们形成同源和异源复合物。它们还通过其N-末端半胱氨酸残基形成六聚体和更高阶的复合物。这些结果表明，像Cbln，C1 ql亚家族具有不同的空间和时间的表达模式，并可能发挥不同的作用，在中枢神经系统中形成同聚体和异聚体复合物。
Many members of the C1q family, including complement C1q and adiponectin, and the structurally related tumor necrosis factor family are secreted and play crucial roles in intercellular signaling. Among them, the Cbln (precerebellin) and C1q-like (C1ql) subfamilies are highly and predominantly expressed in the central nervous system. Although the Cbln subfamily serve as essential trans-neuronal regulators of synaptic integrity in the cerebellum, the functions of the C1ql subfamily (C1ql1-C1ql4) remain unexplored. Here, we investigated the gene expression of the C1ql subfamily in the adult and developing mouse brain by reverse transcriptase-polymerase chain reaction and high-resolution in-situ hybridization. In the adult brain, C1ql1-C1ql3 mRNAs were mainly expressed in neurons but weak expression was seen in glia-like structures in the adult brain. The C1ql1 mRNA was predominantly expressed in the inferior olive, whereas the C1ql2 and C1ql3 mRNAs were strongly coexpressed in the dentate gyrus. Although the C1ql1 and C1ql3 mRNAs were detectable as early as embryonic day 13, the C1ql2 mRNA was observed at later embryonic stages. The C1ql1 mRNA was also expressed transiently in the external granular layer of the cerebellum. Biochemical characterization in heterologous cells revealed that all of the C1ql subfamily proteins were secreted and they formed both homomeric and heteromeric complexes. They also formed hexameric and higher-order complexes via their N-terminal cysteine residues. These results suggest that, like Cbln, the C1ql subfamily has distinct spatial and temporal expression patterns and may play diverse roles by forming homomeric and heteromeric complexes in the central nervous system.