Role of numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2
Role of numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2
复制标题
DOI：
10.1091/mbc.e05-07-0700
复制
发表时间：
2006-03-01
影响因子：
3.3
通讯作者：
Kaibuchi, K
中科院分区：
文献类型：
--
作者：
Nishimura, T;Yamaguchi, T;Kaibuchi, K
在神经系统发育过程中，由于其不对称分配和拮抗Notch信号，Numb与皮层神经发生有关。最近的研究表明，Numb通过结合AP-2复合物在网格蛋白依赖的内吞作用中起作用。Numb也在有丝分裂后神经元中表达，并在轴突生长中起作用。然而，Numb在神经元发育后期的功能尚不清楚。在这里，我们报道了Numb特异性定位于培养的海马神经元的树突棘，并与树突棘的形态发生有关，部分是通过与交叉蛋白的直接相互作用，交叉蛋白是一种Cdc42鸟嘌呤核苷酸交换因子（GEF），作为参与内吞作用和细胞骨架调节的蛋白质的多结构域接头。麻可增强体内Cdc42交叉蛋白的GEF活性。表达Numb或intersectin可导致颈突伸长，而敲低Numb和Numb-like可减少颈突密度和颈突长度。此外，Numb与EphB2受体型酪氨酸激酶和nmda型谷氨酸受体形成复合物。敲低Numb抑制ephrin- b1诱导的脊柱发育和成熟。这些结果强调了Numb在树突棘发育和交叉蛋白和EphB2突触功能中的作用。
Numb has been implicated in cortical neurogenesis during nervous system development, as a result of its asymmetric partitioning and antagonizing Notch signaling. Recent studies have revealed that Numb functions in clathrin-dependent endocytosis by binding to the AP-2 complex. Numb is also expressed in postmitotic neurons and plays a role in axonal growth. However, the functions of Numb in later stages of neuronal development remain unknown. Here, we report that Numb specifically localizes to dendritic spines in cultured hippocampal neurons and is implicated in dendritic spine morphogenesis, partially through the direct interaction with intersectin, a Cdc42 guanine nucleotide exchange factor (GEF) Intersectin functions as a multidomain adaptor for proteins involved in endocytosis and cytoskeletal regulation. Numb enhanced the GEF activity of intersectin toward Cdc42 in vivo. Expression of Numb or intersectin caused the elongation of spine neck, whereas knockdown of Numb and Numb-like decreased the protrusion density and its length. Furthermore, Numb formed a complex with EphB2 receptor-type tyrosine kinase and NMDA-type glutamate receptors. Knockdown of Numb suppressed the ephrin-B1-induced spine development and maturation. These results highlight a role of Numb for dendritic spine development and synaptic functions with intersectin and EphB2.