Polarity-Regulating Kinase Partitioning-Defective 1/Microtubule Affinity-Regulating Kinase 2 Negatively Regulates Development of Dendrites on Hippocampal Neurons
Polarity-Regulating Kinase Partitioning-Defective 1/Microtubule Affinity-Regulating Kinase 2 Negatively Regulates Development of Dendrites on Hippocampal Neurons
复制标题
DOI：
10.1523/jneurosci.3986-07.2007
复制
发表时间：
2007-11
期刊：
影响因子：
--
通讯作者：
T. Terabayashi;T. Itoh;H. Yamaguchi;Yuta Yoshimura;Y. Funato;S. Ohno;H. Miki
中科院分区：
文献类型：
--
作者：
T. Terabayashi;T. Itoh;H. Yamaguchi;Yuta Yoshimura;Y. Funato;S. Ohno;H. Miki
神经元是高度极化的细胞，具有两种形态和功能不同的突起，轴突和树突，分别在神经信号的传递和接收中发挥作用。轴突的定位和引导已经引起了人们的广泛关注，但树突发育的机制大多还不清楚。我们在此报道了一种极性调节蛋白，即分割缺陷蛋白1(Par1b)/微管亲和力调节蛋白2(Mark2)，它特异性地调节海马神经元中树突的发育。Par1b/Mark2的异位表达缩短了树突的长度，减少了树突的分支，但对轴突没有明显影响。RNA干扰下调内源性Par1b/Mark2刺激树突发育。WNT刺激和蓬乱的表达都可以诱导树突的发育，诱导Par1b/Mark2在膜组分上的募集。Par1b/Mark2突变体的表达包含肉豆蔻化信号，并仅聚集在膜上，不影响树突的发育。此外，Par1b/Mark2有效地磷酸化了MAP2，MAP2主要定位在树突中。这些结果表明，Par1b/Mark2通过MAP2的磷酸化负向调节树突的发育。
Neurons are highly polarized cells that possess two morphologically and functionally different types of protrusions, axons and dendrites, that function in the transmission and reception of neural signals, respectively. A great deal of attention has been paid to the specification and guidance of axons, but the mechanism of dendrite development remains mostly unknown. We report here that a polarity-regulating kinase, partitioning-defective 1 (Par1b)/microtubule affinity-regulating kinase 2 (MARK2), specifically regulates development of dendrites in hippocampal neurons. Ectopic expression of Par1b/MARK2 shortens the length and decreases branching of dendrites without significant effects on axons. Knockdown of endogenous Par1b/MARK2 by RNA interference stimulates dendrite development. Wnt stimulation and Dishevelled expression, both of which are known to induce dendrite development, induced recruitment of Par1b/MARK2 to the membrane fraction. Expression of a Par1b/MARK2 mutant, that contains a myristoylation signal and accumulates exclusively in membranes, does not affect dendrite development. In addition, Par1b/MARK2 efficiently phosphorylated MAP2, which is localized mainly in dendrites. These results indicate that Par1b/MARK2 negatively regulates dendrite development through phosphorylation of MAP2.