A novel phenylalanine-based targeting signal directs telencephalin to neuronal dendrites
A novel phenylalanine-based targeting signal directs telencephalin to neuronal dendrites
复制标题
DOI：
10.1523/jneurosci.3853-04.2005
复制
发表时间：
2005-02-02
影响因子：
5.3
通讯作者：
Yoshihara, Y
中科院分区：
文献类型：
--
作者：
Mitsui, S;Saito, M;Yoshihara, Y
神经元将各种功能分子分类到适当的亚细胞目的地。端脑素（TLCN;细胞间粘附分子-5）是特异性定位于端脑神经元中的体树突膜的细胞粘附分子。在这里，我们建立了一个新的在体内的策略来分析神经元的分选机制，异位表达的分子在小脑浦肯野细胞的转基因小鼠。利用该系统，我们在TLCN的胞质尾区鉴定了一个新的树突状靶向决定簇。在浦肯野细胞异位表达的全长TLCN仅定位于树突，而不是轴突。相反，细胞质C-末端12个氨基酸（残基901-912）的缺失或Phe 905到Ala的点突变废除了树突特异性靶向，在轴突和树突中都出现了截短和点突变的TLCN。此外，将TLCN的C-末端17个氨基酸（残基896-912）添加到不相关的分子（CD 8）足以使其特异性靶向几种类型的神经元中的树突。由于TLCN的C-末端区域不包含任何典型的树突靶向序列，如基于酪氨酸的基序或双亮氨酸基序，本研究提出了一种新的蛋白质运输到神经元树突隔室的机制。
Neurons sort out a variety of functional molecules to appropriate subcellular destinations. Telencephalin (TLCN; intercellular adhesion molecule-5) is a cell adhesion molecule specifically localized to somatodendritic membranes in the telencephalic neurons. Here, we established a new in vivo strategy to analyze neuronal sorting mechanisms by ectopic expression of molecules of interest in the cerebellar Purkinje cells of transgenic mice. By using this system, we identified a novel dendritic targeting determinant in the cytoplasmic tail region of TLCN. A full-length TLCN ectopically expressed in the Purkinje cells was localized exclusively to dendrites but not to axons. In contrast, a deletion of cytoplasmic C-terminal 12 amino acids (residues 901-912) or a point mutation of Phe905 to Ala abrogated the dendrite-specific targeting with appearance of the truncated and point-mutated TLCN in both axons and dendrites. Furthermore, an addition of the C-terminal 17 amino acids (residues 896-912) of TLCN to an unrelated molecule (CD8) was sufficient for its specific targeting to dendrites in several types of neurons. Because the C-terminal region of TLCN does not contain any canonical dendritic targeting sequences such as the tyrosine-based motif or the dileucine motif, this study suggests a novel mechanism of protein trafficking to the dendritic compartment of neurons.