Petrone Angiola, Battaglia Fortunato, Wang Cheng, Dusa Adina, Su Jing, Zagzag David, Bianchi Riccardo, Casaccia-Bonnefil Patrizia, Arancio Ottavio, Sap Jan
Department of Pharmacology, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA.
EMBO J. 2003 Aug 15;22(16):4121-31. doi: 10.1093/emboj/cdg399.
Despite clear indications of their importance in lower organisms, the contributions of protein tyrosine phosphatases (PTPs) to development or function of the mammalian nervous system have been poorly explored. In vitro studies have indicated that receptor protein tyrosine phosphatase alpha (RPTPalpha) regulates SRC family kinases, potassium channels and NMDA receptors. Here, we report that absence of RPTPalpha compromises correct positioning of pyramidal neurons during development of mouse hippocampus. Thus, RPTPalpha is a novel member of the functional class of genes that control radial neuronal migration. The migratory abnormality likely results from a radial glial dysfunction rather than from a neuron-autonomous defect. In spite of this aberrant development, basic synaptic transmission from the Schaffer collateral pathway to CA1 pyramidal neurons remains intact in Ptpra(-/-) mice. However, these synapses are unable to undergo long-term potentiation. Mice lacking RPTPalpha also underperform in the radial-arm water-maze test. These studies identify RPTPalpha as a key mediator of neuronal migration and synaptic plasticity.
尽管蛋白酪氨酸磷酸酶（PTPs）在低等生物中的重要性已得到明确证实，但它们对哺乳动物神经系统发育或功能的贡献却鲜有研究。体外研究表明，受体蛋白酪氨酸磷酸酶α（RPTPα）可调节SRC家族激酶、钾通道和NMDA受体。在此，我们报告，在小鼠海马体发育过程中，缺乏RPTPα会影响锥体神经元的正确定位。因此，RPTPα是控制放射状神经元迁移的功能基因类别的一个新成员。迁移异常可能是由放射状胶质细胞功能障碍引起的，而不是神经元自主缺陷所致。尽管存在这种异常发育，在Ptpra(-/-)小鼠中，从谢弗侧支通路到CA1锥体神经元的基本突触传递仍保持完整。然而，这些突触无法进行长时程增强。缺乏RPTPα的小鼠在放射状臂水迷宫试验中的表现也较差。这些研究确定RPTPα是神经元迁移和突触可塑性的关键调节因子。
