Interdepartmental Neuroscience Program, Yale University, New Haven, CT, United States of America.
Department of Psychiatry, Yale University, New Haven, CT, United States of America.
Biochim Biophys Acta Mol Cell Res. 2019 Jan;1866(1):64-73. doi: 10.1016/j.bbamcr.2018.09.006. Epub 2018 Sep 18.
Normal functioning of the brain is dependent upon a complex web of communication between numerous cell types. Within neuronal networks, the faithful transmission of information between neurons relies on an equally complex organization of inter- and intra-cellular signaling systems that act to modulate protein activity. In particular, post-translational modifications (PTMs) are responsible for regulating protein activity in response to neurochemical signaling. The key second messenger, cyclic adenosine 3',5'-monophosphate (cAMP), regulates one of the most ubiquitous and influential PTMs, phosphorylation. While cAMP is canonically viewed as regulating the addition of phosphate groups through its activation of cAMP-dependent protein kinases, it plays an equally critical role in regulating removal of phosphate through indirect control of protein phosphatase activity. This dichotomy of regulation by cAMP places it as one of the key regulators of protein activity in response to neuronal signal transduction throughout the brain. In this review we focus on the role of cAMP in regulation of the serine/threonine phosphatases protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) and the relevance of control of PP1 and PP2A to regulation of brain function and behavior.
大脑的正常功能依赖于众多细胞类型之间复杂的通讯网络。在神经元网络中，神经元之间信息的忠实传递依赖于细胞内和细胞间信号系统同样复杂的组织，这些系统作用是调节蛋白质活性。特别是，翻译后修饰（PTMs）负责调节蛋白质活性以响应神经化学信号。关键的第二信使，环腺苷酸 3'，5'-单磷酸（cAMP），调节最普遍和最有影响力的 PTM 之一，磷酸化。虽然 cAMP 通常被认为通过其激活的 cAMP 依赖性蛋白激酶调节磷酸基团的添加，但它在通过间接控制蛋白磷酸酶活性来调节磷酸基团的去除方面也起着同样关键的作用。这种 cAMP 调节的二分法使其成为大脑中神经元信号转导过程中响应蛋白质活性的关键调节剂之一。在这篇综述中，我们重点介绍 cAMP 在调节丝氨酸/苏氨酸磷酸酶蛋白磷酸酶 1（PP1）和蛋白磷酸酶 2A（PP2A）中的作用，以及对 PP1 和 PP2A 的控制与大脑功能和行为调节的相关性。
