The signaling adaptor protein CD3ζ is a negative regulator of dendrite development in young neurons
The signaling adaptor protein CD3ζ is a negative regulator of dendrite development in young neurons
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DOI：
10.1091/mbc.e07-09-0947
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发表时间：
2008-06-01
影响因子：
3.3
通讯作者：
Boudin, Helene
中科院分区：
文献类型：
--
作者：
Baudouin, Stephane J.;Angibaud, Julie;Boudin, Helene
一个新的想法正在出现，一个大的分子库是共同的神经和免疫系统，这可能反映了新的神经元功能的免疫分子在大脑中的存在。在这里，我们表明，跨膜接头信号蛋白CD3 ζ，首先在免疫系统中描述，有一个以前没有特点的作用，在调节神经元的发育。对大鼠脑和培养神经元的生化和免疫组化分析表明，CD 3 zeta主要在神经元中表达。CD3 zeta在发育中的培养海马神经元中的分布，通过免疫荧光测定，表明CD3 zeta在树突开始分化时优先与体树突隔室相关。在这个阶段，CD3 zeta选择性地集中在树突状丝状伪足和生长锥，肌动蛋白丰富的结构参与神经突的生长和图案。在培养的神经元中siRNA介导的CD3 zeta敲低或在基于免疫受体酪氨酸的激活基序（ITAM）中缺乏酪氨酸磷酸化位点的功能丧失的CD3 zeta突变体的过表达增加树突状分支。相反，通过CD3 zeta抗体激活内源性CD3 zeta降低了树突状乔木的大小。总而言之，我们的研究结果揭示了CD3 zeta在神经系统中的新作用，表明其通过基于ITAM的机制对树突发育的贡献。
A novel idea is emerging that a large molecular repertoire is common to the nervous and immune systems, which might reflect the existence of novel neuronal functions for immune molecules in the brain. Here, we show that the transmembrane adaptor signaling protein CD3 zeta, first described in the immune system, has a previously uncharacterized role in regulating neuronal development. Biochemical and immunohistochemical analyses of the rat brain and cultured neurons showed that CD3 zeta is mainly expressed in neurons. Distribution of CD3 zeta in developing cultured hippocampal neurons, as determined by immunofluorescence, indicates that CD3 zeta is preferentially associated with the somatodendritic compartment as soon as the dendrites initiate their differentiation. At this stage, CD3 zeta was selectively concentrated at dendritic filopodia and growth cones, actin-rich structures involved in neurite growth and patterning. siRNA-mediated knockdown of CD3 zeta in cultured neurons or overexpression of a loss-of-function CD3 zeta mutant lacking the tyrosine phosphorylation sites in the immunoreceptor tyrosine-based activation motifs (ITAMs) increased dendritic arborization. Conversely, activation of endogenous CD3 zeta by a CD3 zeta antibody reduced the size of the dendritic arbor. Altogether, our findings reveal a novel role for CD3 zeta in the nervous system, suggesting its contribution to dendrite development through ITAM-based mechanisms.