Zhang J S, Honkaniemi J, Yang T, Yeo T T, Longo F M
Neurology Service, VA Medical Center, University of California at San Francisco 94121, USA.
Mol Cell Neurosci. 1998 Apr;10(5-6):271-86. doi: 10.1006/mcne.1998.0663.
Transgenic mice and Drosophila mutant studies demonstrate that the leukocyte common antigen-related (LAR) protein tyrosine phosphatase (PTPase) receptor is required for formation of neural networks. We assessed the hypothesis that alternative splicing of the LAR extracellular region contributes to this function by establishing temporospatial expression patterns of LAR isoforms containing an alternatively spliced extracellular nine amino acid segment (LAR alternatively spliced element-c; LASE-c). LASE-c was present in multiple alternatively spliced and truncated LAR transcripts. In contrast to LAR isoforms without LASE-c, levels of LAR transcripts and protein isoforms containing LASE-c were primarily present during development, suggesting a mechanism for developmental regulation of LAR function. In situ analysis demonstrated increasingly region- and cell-specific expression of LASE-c during maturation. Immunostaining revealed LASE-c-containing LAR protein along neurites and in growth cones. The discovery of highly regulated, temporospatial extracellular domain alternative splicing of LAR-type PTPase receptors points to a novel mechanism by which these receptors might influence network formation.
转基因小鼠和果蝇突变体研究表明,白细胞共同抗原相关(LAR)蛋白酪氨酸磷酸酶(PTPase)受体对于神经网络的形成是必需的。我们通过建立含有选择性剪接的细胞外九个氨基酸片段(LAR选择性剪接元件-c;LASE-c)的LAR异构体的时空表达模式,评估了LAR细胞外区域的选择性剪接有助于此功能的假说。LASE-c存在于多个选择性剪接和截短的LAR转录本中。与不含LASE-c的LAR异构体相反,含有LASE-c的LAR转录本和蛋白质异构体水平主要在发育过程中出现,提示了一种LAR功能发育调控的机制。原位分析表明,在成熟过程中LASE-c的区域和细胞特异性表达不断增加。免疫染色显示,沿神经突和生长锥存在含有LASE-c的LAR蛋白。LAR型PTPase受体高度调控的时空细胞外结构域选择性剪接的发现,指出了这些受体可能影响网络形成的一种新机制。