Fischer André, Sananbenesi Farahnaz, Spiess Joachim, Radulovic Jelena
Laboratory on Cell Biologic Mechanisms of Memory, Department of Molecular Neuroendocrinology, Max Planck Institute for Experimental Medicine, Göttingen, Germany.
Neurosignals. 2003 Sep-Oct;12(4-5):200-8. doi: 10.1159/000074621.
Learning and memory are processes by which organisms acquire, retain and retrieve information. They result in modifications of behavior in response to new or previously encountered stimuli thereby enabling adaptation to a permanently changing environment. Protein phosphorylation has long been known to play a key role in triggering synaptic changes underlying learning and memory. Although intracellular phosphorylation and dephosphorylation is orchestrated by a complex network of interactions between a number of protein kinases and phosphatases, significant advances in the understanding of neuronal mechanisms underlying learning and memory have been achieved by investigating the actions of individual molecules under defined experimental conditions, brain areas, neuronal cells and their subcellular compartments. On the basis of these approaches, the cyclic AMP protein kinase (PKA), protein kinase C (PKC) and extracellularly regulated protein kinases 1 and 2 (Erk-1/2) have been identified as the core signaling pathways in memory consolidation. Here we review recent findings demonstrating an important novel role for Cdk5 in learning and memory. We suggest that some of the well-characterized roles of Cdk5 during neurodevelopmental processes, such as interactions with distinct cytoplasmic and synaptic target molecules, may be also involved in synaptic plasticity underlying memory consolidation within the adult central nervous system.
学习和记忆是生物体获取、保留和检索信息的过程。它们导致生物体对新的或先前遇到的刺激做出行为改变,从而使其能够适应不断变化的环境。长期以来,人们一直认为蛋白质磷酸化在触发学习和记忆背后的突触变化中起关键作用。尽管细胞内的磷酸化和去磷酸化是由许多蛋白激酶和磷酸酶之间复杂的相互作用网络协调的,但通过在特定实验条件、脑区、神经元细胞及其亚细胞区室中研究单个分子的作用,人们在理解学习和记忆背后的神经元机制方面取得了重大进展。基于这些方法,环磷酸腺苷蛋白激酶(PKA)、蛋白激酶C(PKC)以及细胞外调节蛋白激酶1和2(Erk-1/2)已被确定为记忆巩固中的核心信号通路。在此,我们综述了最近的研究结果,这些结果表明细胞周期蛋白依赖性激酶5(Cdk5)在学习和记忆中具有重要的新作用。我们认为,Cdk5在神经发育过程中的一些已被充分描述的作用,比如与不同的细胞质和突触靶分子的相互作用,可能也参与了成体中枢神经系统内记忆巩固所依赖的突触可塑性。