C. elegans STRADα and SAD cooperatively regulate neuronal polarity and synaptic organization
C. elegans STRADα and SAD cooperatively regulate neuronal polarity and synaptic organization
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DOI：
10.1242/dev.041459
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发表时间：
2010-01-01
期刊：
影响因子：
4.6
通讯作者：
Zhen, Mei
中科院分区：
文献类型：
--
作者：
Kim, Joanne S. M.;Hung, Wesley;Zhen, Mei
神经元是具有形态和功能不同的轴突和树突的极化细胞。SAD激酶对于建立跨物种的轴突-树突身份至关重要。先前的研究表明，肿瘤抑制激酶LKB 1在假激酶STRAD α存在下，通过激活脊椎动物神经元中的SAD激酶来启动轴突分化和生长。在各种细胞培养研究中，STRAD α与LKB 1的定位、稳定和活化有关。然而，其在体内的功能尚未被检查。在我们目前的研究中，我们分析了STRAD α第一个功能丧失突变体的神经元表型，并检查了它们与C中LKB 1和SAD的遗传相互作用。优美的出乎意料的是，只有C。线虫STRAD α，STRD-1，专门通过SAD激酶SAD-1发挥作用，调节神经元极性和突触组织。此外，STRD-1与SAD-1紧密结合以协调其突触定位。相比之下，C.秀丽线虫LKB 1，PAR-4，也独立于SAD-1和STRD-1在另外的遗传途径中起作用以调节神经元极性。我们建议，STRD-1建立神经元极性和组织突触蛋白在一个复杂的SAD-1激酶。我们的研究结果表明，而不是一个单一的，线性的遗传途径，STRAD α和LKB 1调节神经元的发展，通过多种效应器，在某些细胞环境中共享，但在其他不同。
Neurons are polarized cells with morphologically and functionally distinct axons and dendrites. The SAD kinases are crucial for establishing the axon-dendrite identity across species. Previous studies suggest that a tumour suppressor kinase, LKB1, in the presence of a pseudokinase, STRAD alpha, initiates axonal differentiation and growth through activating the SAD kinases in vertebrate neurons. STRAD alpha was implicated in the localization, stabilization and activation of LKB1 in various cell culture studies. Its in vivo functions, however, have not been examined. In our present study, we analyzed the neuronal phenotypes of the first loss-of-function mutants for STRAD alpha and examined their genetic interactions with LKB1 and SAD in C. elegans. Unexpectedly, only the C. elegans STRAD alpha, STRD-1, functions exclusively through the SAD kinase, SAD-1, to regulate neuronal polarity and synaptic organization. Moreover, STRD-1 tightly associates with SAD-1 to coordinate its synaptic localizations. By contrast, the C. elegans LKB1, PAR-4, also functions in an additional genetic pathway independently of SAD-1 and STRD-1 to regulate neuronal polarity. We propose that STRD-1 establishes neuronal polarity and organizes synaptic proteins in a complex with the SAD-1 kinase. Our findings suggest that instead of a single, linear genetic pathway, STRAD alpha and LKB1 regulate neuronal development through multiple effectors that are shared in some cellular contexts but distinct in others.