Role of LKB1-SAD/MARK Pathway in Neuronal Polarization
Role of LKB1-SAD/MARK Pathway in Neuronal Polarization
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DOI：
10.1002/dneu.20884
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发表时间：
2011-06-01
影响因子：
3
通讯作者：
Poo, Mu-Ming
中科院分区：
文献类型：
--
作者：
Shelly, Maya;Poo, Mu-Ming
轴突/树突极性的形成对于神经元在大脑中执行其信号功能至关重要。分离海马神经元的培养系统极大地促进了我们对神经元极性发展和维持的细胞和分子机制的理解。在许多与极化相关的蛋白质中，我们在这里重点关注哺乳动物的LKB1，它是秀丽隐杆线虫Par-4的对应物，它是六个Par（分裂缺陷）基因中的上游调节剂，在进化遥远的物种中不同细胞类型中充当细胞极性的主要调节剂。最近的研究发现LKB1及其下游靶点SAD/MARK激酶（哺乳动物Par-1的同源物）是培养神经元和体内皮质神经元中神经元极化和轴突发育的关键调节因子。我们将根据从神经元和非神经元系统获得的信息，回顾LKB1-SAD/MARK通路中蛋白质的特性和相互作用。由于LKB1蛋白激酶A依赖性磷酸化在该通路的激活中起着核心作用，我们将回顾最近的研究结果，包括cAMP和cGMP信号如何作为轴突/树突发育的拮抗第二信使，以及这些环核苷酸如何通过调节LKB1- sad /MARK通路的活性来介导细胞外极化因子的作用。(C) 2011 Wiley期刊公司中国生物医学工程学报（英文版），2011
The formation of axon/dendrite polarity is critical for the neuron to perform its signaling function in the brain. Recent advance in our understanding of cellular and molecular mechanisms underlying the development and maintenance of neuronal polarity has been greatly facilitated by the use of the culture system of dissociated hippocampal neurons. Among many polarization-related proteins, we here focus on the mammalian LKB1, the counterpart of the C. elegans Par-4, which is an upstream regulator among six Par (partitioning-defective) genes that act as master regulators of cell polarity in different cell types across evolutionary distant species. Recent studies have identified LKB1 and its downstream targets SAD/MARK kinases (mammalian homologs of Par-1) as key regulators of neuronal polarization and axon development in cultured neurons and in developing cortical neurons in vivo. We will review the properties of and interactions among proteins in this LKB1-SAD/MARK pathway, drawing upon information obtained from both neuronal and non-neuronal systems. Due to central role of the protein kinase A - dependent phosphorylation of LKB1 in the activation of this pathway, we will review recent findings on how cAMP and cGMP signaling may serve as antagonistic second messengers for axon/dendrite development, and how these cyclic nucleotides may mediate the action of extracellular polarizing factors by modulating the activity of the LKB1-SAD/MARK pathway. (C) 2011 Wiley Periodicals, Inc. Develop Neurobiol 71: 508-527, 2011