Ror1-Ror2 complexes modulate synapse formation in hippocampal neurons.
Ror1-Ror2 complexes modulate synapse formation in hippocampal neurons.
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DOI：
10.1016/j.neuroscience.2009.11.056
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发表时间：
2010-02-17
期刊：
影响因子：
3.3
通讯作者：
Ferreira A
中科院分区：
文献类型：
--
作者：
Paganoni S;Bernstein J;Ferreira A
ROR1和Ror2是酪氨酸激酶受体的一个小家族，与线虫和莱维氏X.laevis的大脑发育的多个方面有关。最近，我们已经证明这些受体调节培养的大鼠海马神经元的轴突伸长速度。然而，目前还没有关于这些受体在哺乳动物中枢神经元其他发育里程碑中的潜在作用的信息。ROR配体(S)的身份和/或他们参与的信号转导途径(S)的身份也不清楚。在这里，我们报告了Ror1或Ror2的下调导致培养的海马神经元突触形成显著减少。然而，同时靶向RoR蛋白并没有导致相加的表型。我们的结果还表明，Ror1和Ror2在小鼠大脑中存在物理上的相互作用，这表明它们可能在中枢神经元中作为异源二聚体发挥作用。此外，这些ROR复合体还与WNT-5a相互作用，介导其对突触发生的影响。综上所述，这些数据表明，Ror蛋白在Wnt-5a激活的信号通路中发挥关键作用，导致哺乳动物中枢神经系统中突触的形成。
Ror1 and Ror2, a small family of tyrosine kinase receptors, have been implicated in multiple aspects of brain development in C. elegans and X. laevis. More recently, we have shown that these receptors modulate the rate of neurite elongation in cultured rat hippocampal neurons. However, no information is available regarding a potential role of these receptors in other developmental milestones in mammalian central neurons. Neither is the identity known of the Ror ligand(s) and/or the signal transduction pathway(s) in which they participate. Here we report that the down regulation of either Ror1 or Ror2 led to a significant decrease in synapse formation in cultured hippocampal neurons. Simultaneous targeting of Ror proteins, however, did not result in an additive phenotype. Our results also indicated that Ror1 and Ror2 physically interact in the mouse brain, suggesting that they might function as heterodimers in central neurons. In addition, these Ror complexes interacted with Wnt-5a mediating its effects on synaptogenesis. Together, these data suggest that Ror proteins play a key role in Wnt-5a-activated signaling pathways leading to synapse formation in the mammalian central nervous system.
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影响因子：
64.8
作者：
Bhanot, P;Brink, M;Nusse, R
通讯作者：
Nusse, R
DOI：
10.1016/0165-3806(89)90023-0
发表时间：
1989-10-01
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
FERREIRA, A;BUSCIGLIO, J;CACERES, A
通讯作者：
CACERES, A
影响因子：
5.3
作者：
Keeble, Thomas R.;Halford, Michael M.;Cooper, Helen M.
通讯作者：
Cooper, Helen M.
DOI：
10.1073/pnas.76.1.514
发表时间：
1979-01-01
影响因子：
11.1
作者：
BOTTENSTEIN, JE;SATO, GH
通讯作者：
SATO, GH
影响因子：
64.5
作者：
Glass, DJ;Bowen, DC;Yancopoulos, GD
通讯作者：
Yancopoulos, GD