Compartmentalization of adenylate cyclase and cAMP signalling
Compartmentalization of adenylate cyclase and cAMP signalling
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DOI：
10.1042/bst0331319
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发表时间：
2005-12-01
影响因子：
3.9
通讯作者：
Cooper, DMF
中科院分区：
文献类型：
--
作者：
Cooper, DMF
cAMP信号传导的概念已经从几年前的线性级联发生了巨大的变化，人们认识到许多细胞过程都会影响这个基序。这些影响包括其他信号传导途径-最重要的是Ca 2+，支架蛋白（其本身受到不同的调节）组织途径的元素，以及组分的亚细胞靶向。这种组织的一个明显的含义是，cAMP的全球测量可能会使cAMP信号的复杂性变得微不足道，并使靶点的调节变得模糊。在本报告中，目前的发展目标和组装的AC（腺苷酸环化酶）和它们的交付选定的筏或非筏结构域的质膜将被讨论，沿着与筏靶向AC的敏感性非常离散的模式增加细胞内的钙离子浓度。本文还描述了用环核苷酸门控通道测量的cAMP动力学的单细胞探索，特别是应用于AKAP（A-激酶锚定蛋白）-PKA（蛋白激酶A）-PDE（磷酸二酯酶）组件的组合物通过RNA干扰消融确定的AKAP来探测的细胞。
Concepts of cAMP signalling have changed dramatically from the linear cascades of just a few years ago, with the realization that numerous cellular processes affect this motif. These influences include other signalling pathways - most significantly Ca2+, scaffolding proteins (which are themselves variously regulated) to organize the elements of the pathway, and subcellular targeting of components. An obvious implication of this organization is that global measurements of cAMP may trivialize the complexity of the cAMP signals and obscure the regulation of targets. In this presentation, current developments on the targeting and assembly of ACs (adenylate cyclases) and their delivery to selected raft or non-raft domains of the plasma membrane will be discussed, along with the susceptibility of raft-targeted ACs to very discrete modes of increases in the intracellular Ca2+ concentration. Single-cell explorations of cAMP dynamics, as measured with cyclic nucleotide-gated channels, are also described in this paper, particularly as applied to cells in which the composition of AKAP (A-kinase anchoring protein)-PKA (protein kinase A)-PDE (phosphodiesterase) assemblies is probed by RNA interference ablation of defined AKAPs.