Shima Yasuyuki, Kawaguchi Shin-ya, Kosaka Kazuyoshi, Nakayama Manabu, Hoshino Mikio, Nabeshima Yoichi, Hirano Tomoo, Uemura Tadashi
Graduate School of Biostudies, Yoshida Konoecho, Kyoto University, Kyoto, Kyoto 606-8501, Japan.
Nat Neurosci. 2007 Aug;10(8):963-9. doi: 10.1038/nn1933. Epub 2007 Jul 8.
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.
在神经系统发育过程中，众多神经元及其神经突紧密排列，神经突（轴突和树突）的生长应通过它们之间的相互作用得到适当调节。我们在此表明，哺乳动物七次跨膜钙黏蛋白Celsr2和Celsr3通过其嗜同性相互作用被激活，并以相反的方式调节神经突生长。基因沉默实验以及与大鼠神经元培养物的共培养实验均表明，Celsr2促进神经突生长，而Celsr3抑制神经突生长，并且它们相反的功能很可能是由跨膜结构域中单个氨基酸残基的差异导致的。结合钙成像和药理学分析，我们的结果表明，Celsr2和Celsr3通过第二信使发挥其功能，并且同源物活性的差异在神经突生长调节中产生相反的作用。
