PROTEIN CARBOXYL METHYLATION IN BRAIN

这个项目的总体目标是探索蛋白质羧基的作用。 甲基化在突触和神经元功能调节中的作用。羧基 甲基化被认为在蛋白质的调节中起着重要作用。 功能，特别是在神经和内分泌组织中。一个被广泛接受的 Model将羧甲基化视为蛋白质的可逆修饰 功能类似于磷酸化-去磷酸化，但有 这个简单的模型有几个不一致之处。它最近被发现了 羧甲基化不是可逆反应，而是它 是复杂反应的第一步，它会释放未甲基化的 与原始底物不同的多肽，不能 重新甲基化。这一发现对体内研究具有重要意义。 羧甲基化的功能，并提出了一种新的方法 需要对这种酶进行分析，以正确评估其在调节中的作用 事件。当前提案的一个直接目标是确定 蛋白质羧基催化的异常多肽修饰的性质 甲基转移酶。另一个目标是使用甲醇生成试验来 在脑亚成分中寻找这种酶的内源底物 组织，并评估这种反应受 跨膜信号，如去极化和神经递质受体 激活，或通过细胞内信号，如cAMP、cGMP和Ca++。这 研究将大大提高我们对生物化学的理解。 神经元和突触活动调节不足的机制 哺乳动物的大脑。

The overall goal of this project is to explore the role of protein carboxyl methylation in regulation of synaptic and neuronal function. Carboxyl methylation is believed to play an important role in modulation of protein function, particularly in neural and endocrine tissues. A widely accepted model views carboxyl methylation as a reversible modification of protein function analogous to phosphorylation-dephosphorylation, yet there are several inconsistencies with this simple model. It has recently been found that carboxyl methylation is not a reversible reaction, but rather that it is the first step in a complex reaction which releases an unmethylated peptide that is different from the original substrate and cannot be remethylated. This finding has important implications for the in vivo function of carboxyl methylation and suggests that a new approach to assaying this enzyme is needed to properly evaluate its role in regulatory events. One immediate aim of the current proposal is to determine the nature of the unusual peptide modification catalyzed by protein carboxyl methyltransferase. Another aim is to use a methanol formation assay to search for endogenous substrates for this enzyme in subfractions of brain tissue and to evaluate the possibility that this reaction is modulated by transmembrane signals such as depolarization and neurotransmitter receptor activation, or by intracellular signals such as cAMP, cGMP and Ca++. This research sould substantially improve our understanding of the biochemical mechanisms which underly regulation of neuronal and synaptic activity in the mammalian brain.