Protein tyrosine phosphatase receptor type Z is involved in hippocampus-dependent memory formation through dephosphorylation at Y1105 on p190 RhoGAP
Protein tyrosine phosphatase receptor type Z is involved in hippocampus-dependent memory formation through dephosphorylation at Y1105 on p190 RhoGAP
复制标题
DOI：
10.1016/j.neulet.2006.01.045
复制
发表时间：
2006-05-15
影响因子：
2.5
通讯作者：
Noda, Masaharu
中科院分区：
文献类型：
--
作者：
Tamura, Hiroshi;Fukada, Masahide;Noda, Masaharu
Ptprz是一种受体型蛋白酪氨酸磷酸酶，主要在脑中作为硫酸软骨素蛋白聚糖表达。Ptprz缺陷小鼠在Morris水迷宫试验中表现出年龄（成熟）依赖性的空间学习障碍，并在海马切片中CA I区表现出长时程增强（LTP）。增强的LTP被Rho相关激酶（ROCK）的药理学抑制所抵消，这表明Ptprz的缺乏由于ROCK的异常激活而导致学习障碍。在这里，我们报告说，Ptprz缺陷小鼠表现出的障碍，因为异常的酪氨酸磷酸化的p190 RhoGAR一个GTP酶激活蛋白（GAP）的Rho GTP酶依赖的背景恐惧记忆。我们发现，磷酸化Y1105，一个主要的酪氨酸磷酸化位点的p190 RhoGAP，是减少后，在野生型小鼠的海马调节，但不是Ptprz缺陷型小鼠。Pleiotrophin是Ptprz的配体，可增加B103神经母细胞瘤细胞中p190 RhoGAP的酪氨酸磷酸化。此外，Ptprz在体外选择性地使p190 RhoGAP的pY1105去磷酸化，而Y1105处的酪氨酸磷酸化控制体内p190 RhoGAP的活性。这些结果表明Ptprz通过Y1 105 oil p190 RhoGAR（c）2006 Elsevier爱尔兰有限公司的去磷酸化来调节Rho GTPase活性，在记忆形成中发挥关键作用。保留所有权利。
Ptprz is a receptor-type protein tyrosine phosphatase predominantly expressed in the brain as a chondroitin sulfate proteoglycan. Ptprz-deficient mice exhibit an age (maturation)-dependent impairment of spatial learning in the Morris water maze test and enhancement of long-term potentiation (LTP) in the CA I region in hippocampal slices. The enhanced LTP is canceled out by pharmacological inhibition of Rho-associated kinase (ROCK), suggesting that the lack of Ptprz causes learning impairment due to aberrant activation of ROCK. Here, we report that Ptprz-deficient mice exhibit impairments in hippocampus-dependent contextual fear memory because of abnormal tyrosine phosphorylation of p190 RhoGAR a GTPase-activating protein (GAP) for Rho GTPase. We found that phosphorylation at Y1105, a major tyrosine phosphorylation site on p190 RhoGAP, is decreased I It after the conditioning in the hippocampus of wild-type mice, but not of Ptprz-deficient mice. Pleiotrophin, a ligand for Ptprz, increased tyrosine phosphorylation of p190 RhoGAP in B103 neuroblastoma cells. Furthermore, Ptprz selectively dephosphorylated pY1 105 of p190 RhoGAP in vitro, and the tyrosine phosphorylation at Y1 105 controls p190 RhoGAP activity in vivo. These results Suggest that Ptprz plays a critical role in memory formation by modulating Rho GTPase activity through dephosphorylation at Y1 105 oil p190 RhoGAR (c) 2006 Elsevier Ireland Ltd. All rights reserved.