Bretin Sylvie, Rogemond Véronique, Marin Philippe, Maus Marion, Torrens Yvette, Honnorat Jérôme, Glowinski Jacques, Prémont Joël, Gauchy Christian
INSERM, Collège de France, Paris, France.
J Neurochem. 2006 Aug;98(4):1252-65. doi: 10.1111/j.1471-4159.2006.03969.x. Epub 2006 Jun 19.
The brain is particularly vulnerable to ischaemia; however, neurons can become tolerant to ischaemic insult. This tolerance has been shown to involve activation of NMDA receptors, but its mechanisms have not yet been fully elucidated. Using a preconditioning protocol, we show that neurons surviving to a transient NMDA exposure become resistant to the glutamatergic agonist. Using a proteomic approach, we found that alterations of the protein pattern of NMDA-resistant neurons are restricted mainly to the five collapsin response mediator proteins (CRMPs). A sustained increase in calpain activity following NMDA treatment is responsible for the production of cleaved CRMPs. Finally, we provide evidence for the involvement of the cleaved form of WT-CRMP2 in the down-regulation of NR2B. Our data suggests that, beside their role in neuronal morphogenesis, CRMPs may contribute to neuronal plasticity.
大脑对缺血特别敏感；然而，神经元可以对缺血性损伤产生耐受性。这种耐受性已被证明涉及N-甲基-D-天冬氨酸（NMDA）受体的激活，但其机制尚未完全阐明。通过预处理方案，我们发现经历短暂NMDA暴露后存活的神经元对谷氨酸能激动剂产生抗性。使用蛋白质组学方法，我们发现NMDA抗性神经元的蛋白质模式改变主要局限于五种塌陷反应介导蛋白（CRMPs）。NMDA处理后钙蛋白酶活性的持续增加导致了裂解的CRMPs的产生。最后，我们提供了证据表明WT-CRMP2的裂解形式参与了NR2B的下调。我们的数据表明，除了它们在神经元形态发生中的作用外，CRMPs可能有助于神经元可塑性。
