Poser S, Storm D R
Department of Pharmacology, University of Washington, Health Sciences Building, Mail Box 357750, Seattle, WA 98195-7750, USA.
Int J Dev Neurosci. 2001 Jul;19(4):387-94. doi: 10.1016/s0736-5748(00)00094-0.
Studies with invertebrates and vertebrates have strongly implicated the CREB/CRE transcriptional pathway in long-term memory (LTM) and transcriptionally-dependent L-LTP. It is hypothesized that LTM and L-LTP are both dependent upon a Ca2+ signal generated through activation of NMDA receptors. This review discusses evidence that Ca2+ signals generated through activation of NMDA receptors coactivate the Erk/MAP kinase and cAMP signal transduction pathways. It is hypothesized that activation of these two regulatory pathways increases the transcription of a family of genes through the CREB/CRE transcriptional pathway. Gene disruption studies have shown that Ca2+ activated adenylyl cyclases play a critical role in generating the cAMP signal required for LTM and L-LTP. Although cAMP may be required for several events in this complex signal transduction cascade, one of the major roles of cAMP may be to support nuclear translocation of Erk/MAP kinase in hippocampal neurons.
对无脊椎动物和脊椎动物的研究有力地表明，CREB/CRE转录途径与长期记忆（LTM）以及转录依赖性长时程增强（L-LTP）有关。据推测，LTM和L-LTP均依赖于通过N-甲基-D-天冬氨酸（NMDA）受体激活产生的Ca2+信号。本综述讨论了通过NMDA受体激活产生的Ca2+信号共同激活细胞外信号调节激酶/丝裂原活化蛋白激酶（Erk/MAP激酶）和环磷酸腺苷（cAMP）信号转导途径的证据。据推测，这两条调节途径的激活通过CREB/CRE转录途径增加了一组基因的转录。基因敲除研究表明，Ca2+激活的腺苷酸环化酶在产生LTM和L-LTP所需的cAMP信号中起关键作用。尽管cAMP可能是这个复杂信号转导级联反应中多个事件所必需的，但cAMP的主要作用之一可能是支持海马神经元中Erk/MAP激酶的核转位。
