Opposing roles in neurite growth control by two 7-pass transmembrane cadherins
Opposing roles in neurite growth control by two 7-pass transmembrane cadherins
复制标题
两种七次跨膜钙粘蛋白在神经突生长控制中的相反作用
DOI：
10.1038/nn1933
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发表时间：
2007
影响因子：
25
通讯作者：
Uemura T
中科院分区：
文献类型：
--
作者：
Shima Y;Kawaguchi SY;Kosaka K;Nakayama M;Hoshino M;Nabeshima Y;Hirano T;Uemura T
在神经系统的发育过程中，神经突起(轴突和树突)的生长应受到它们相互作用的适当调节。在神经系统中，无数的神经元及其突起紧密堆积在一起。我们在这里表明，哺乳动物的七次跨膜钙粘附素Celsr2和Celsr3被它们的同嗜性相互作用激活，并以相反的方式调节轴突生长。基因沉默和与大鼠神经元培养的共培养实验都表明，Celsr2促进轴突生长，而Celsr3抑制轴突生长，两者相反的功能很可能是由于跨膜区中单一氨基酸残基的不同所致。结合钙离子成像和药理学分析，我们的结果表明Celsr2和Celsr3通过第二信使发挥其功能，而同系物活性的不同导致了对轴突生长调节的相反作用。
The growth of neurites (axon and dendrite) should be appropriately regulated by their interactions in the development of nervous systems where a myriad of neurons and their neurites are tightly packed. We show here that mammalian seven-pass transmembrane cadherins Celsr2 and Celsr3 are activated by their homophilic interactions and regulate neurite growth in an opposing manner. Both gene-silencing and coculture assay with rat neuron cultures showed that Celsr2 enhanced neurite growth, whereas Celsr3 suppressed it, and that their opposite functions were most likely the result of a difference of a single amino acid residue in the transmembrane domain. Together with calcium imaging and pharmacological analyses, our results suggest that Celsr2 and Celsr3 fulfill their functions through second messengers, and that differences in the activities of the homologs results in opposite effects in neurite growth regulation.