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首页> 外文期刊>Molecular biology of the cell >p250GAP, a novel brain-enriched GTPase-activating protein for Rho family GTPases, is involved in the N-methyl-D-aspartate receptor signaling
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p250GAP, a novel brain-enriched GTPase-activating protein for Rho family GTPases, is involved in the N-methyl-D-aspartate receptor signaling

机译：p250GAP是一种针对Rho家族GTPases的新型大脑富集GTPase激活蛋白，参与N-甲基-D-天冬氨酸受体信号传导

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摘要

N-Methyl-D-aspartate (NMDA) receptors regulate structural plasticity by modulating actin organization within dendritic spines. Herein, we report identification and characterization of p250GAP, a novel GTPase-activating protein for Rho family proteins that interacts with the GluRepsilon2 (NR2B) subunit of NMDA receptors in vivo. The p250GAP mRNA was enriched in brain, with high expression in cortex, corpus striatum, hippocampus, and thalamus. Within neurons, p250GAP was highly concentrated in the postsynaptic density and colocalized with the GluRepsilon2 (NR2B) subunit of NMDA receptors and with postsynaptic density-95. p250GAP promoted GTP hydrolysis of Cdc42 and RhoA in vitro and in vivo. When overexpressed in neuroblastoma cells, p250GAP suppressed the activities of Rho family proteins, which resulted in alteration of neurite outgrowth. Finally, NMDA receptor stimulation led to dephosphorylation and redistribution of p250GAP in hippocampal slices. Together, p250GAP is likely to be involved in NMDA receptor activity-dependent actin reorganization in dendritic spines. [References: 65]
机译：N-甲基-D-天冬氨酸（NMDA）受体通过调节树突棘内的肌动蛋白组织来调节结构可塑性。在本文中，我们报道了p250GAP的鉴定和表征，p250GAP是一种Rho家族蛋白的新型GTPase激活蛋白，与体内NMDA受体的GluRepsilon2（NR2B）亚基相互作用。 p250GAP mRNA在大脑中富集，在皮质，纹状体，海马和丘脑中高表达。在神经元内，p250GAP高度集中在突触后密度中，并与NMDA受体的GluRepsilon2（NR2B）亚基共定位，并与突触后密度为95。 p250GAP在体外和体内都促进了Cdc42和RhoA的GTP水解。当在神经母细胞瘤细胞中过表达时，p250GAP会抑制Rho家族蛋白的活性，从而导致神经突增生的改变。最后，NMDA受体刺激导致海马切片中p250GAP的去磷酸化和重新分布。总之，p250GAP可能参与树突棘中NMDA受体活性依赖性肌动蛋白的重组。 [参考：65]

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