Identification and characterization of Slitrk, a novel neuronal transmembrane protein family controlling neurite outgrowth

Identification and characterization of Slitrk, a novel neuronal transmembrane protein family controlling neurite outgrowth
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DOI:
10.1016/s1044-7431(03)00129-5
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发表时间:
2003-09-01
影响因子:
3.5
通讯作者:
Mikoshiba, K
Mikoshiba, K
中科院分区:
医学3区
文献类型:
--
作者:
Aruga, J;Mikoshiba, K

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Slitrk家族由小鼠中六种结构相关的跨膜蛋白(Slitrk 1 -6)组成。在细胞外区域,它们共有两个保守的富含亮氨酸的重复结构域,该结构域与分泌的轴突生长控制蛋白Slit具有显着的同源性。这些蛋白质在其胞内结构域中也与trk神经营养因子受体具有同源性,共享保守的酪氨酸残基。Slitrk的表达高度局限于神经组织,但在家族内变化。更具体地说,Slitrk 1表达在成熟神经元中,而Slitrk 2在心室层中强烈表达,Slitrk 6在间脑中显示区室化表达。过表达Slitrk 1诱导单极神经突起在培养的神经元细胞,而Slitrk 2和其他Slitrk蛋白抑制神经突起的生长。缺失分析表明,Slitrk 1和Slitrk 2之间的功能差异在于它们的胞内结构域,这些结构域在Slitrk 2 -6中是保守的,而在Slitrk 1中不是。这些结果表明,Slitrk蛋白是控制神经突生长的神经元成分。(C)2003 Elsevier Science(美国)。All rights reserved.
The Slitrk family consists of six structurally related transmembrane proteins (Slitrk1-6) in the mouse. In the extracellular region, they share two conserved leucine-rich repeat domains that have a significant homology to a secreted axonal growth-controlling protein, Slit. These proteins also have a homology to trk neurotrophin receptors in their intracellular domains, sharing a conserved tyrosine residue. Expression of Slitrk is highly restricted to neural tissues, but varies within the family. More specifically, Slitrk1 expression is in the mature neurons, whereas Slitrk2 is strongly expressed in the ventricular layer, and Slitrk6 shows compartmentalized expression in diencephalon. Over-expressed Slitrk1 induced unipolar neurites in cultured neuronal cells, whereas Slitrk2 and other Slitrk proteins inhibited neurite outgrowth. Deletion analysis showed that the functional difference between Slitrk1 and Slitrk2 lies in their intracellular domains, which are conserved in Slitrk2-6, but not in Slitrk1. These results suggest that the Slitrk proteins are the neuronal components that control the neurite outgrowth. (C) 2003 Elsevier Science (USA). All rights reserved.