A chemical-genetic strategy reveals distinct temporal requirements for SAD-1 kinase in neuronal polarization and synapse formation.
A chemical-genetic strategy reveals distinct temporal requirements for SAD-1 kinase in neuronal polarization and synapse formation.
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DOI：
10.1186/1749-8104-3-23
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发表时间：
2008-09-22
影响因子：
3.6
通讯作者：
Zhen M
中科院分区：
文献类型：
--
作者：
Kim JS;Lilley BN;Zhang C;Shokat KM;Sanes JR;Zhen M
神经元通过一系列发育过程组装成功能网络，包括神经元极化和突触形成。在秀丽隐杆线虫中，丝氨酸/苏氨酸SAD-1激酶对于适当的神经元极性和突触组织是必需的。为了确定SAD-1活性是否调节这些神经元结构的建立或维持，我们使用化学遗传学方法研究了其时间要求，该方法允许其激酶活性在体内的选择性和可逆性失活。我们产生了SAD-1的PP 1类似物敏感变体。通过SAD-1激酶活性的时间抑制，我们发现它的活性是建立神经元极性和突触组织所必需的。然而，虽然SAD-1活性是严格需要当神经元极化，SAD-1的时间要求是不太严格的突触组织，这也可以在维护过程中重新建立。本研究报告的第一个时间分析的神经激酶活性的化学遗传系统。这表明神经元极性和突触组织对SAD-1有不同的时间要求。
Neurons assemble into a functional network through a sequence of developmental processes including neuronal polarization and synapse formation. In Caenorhabditis elegans, the serine/threonine SAD-1 kinase is essential for proper neuronal polarity and synaptic organization. To determine if SAD-1 activity regulates the establishment or maintenance of these neuronal structures, we examined its temporal requirements using a chemical-genetic method that allows for selective and reversible inactivation of its kinase activity in vivo. We generated a PP1 analog-sensitive variant of SAD-1. Through temporal inhibition of SAD-1 kinase activity we show that its activity is required for the establishment of both neuronal polarity and synaptic organization. However, while SAD-1 activity is needed strictly when neurons are polarizing, the temporal requirement for SAD-1 is less stringent in synaptic organization, which can also be re-established during maintenance. This study reports the first temporal analysis of a neural kinase activity using the chemical-genetic system. It reveals that neuronal polarity and synaptic organization have distinct temporal requirements for SAD-1.
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DOI：
10.1083/jcb.200309096
发表时间：
2004-01-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ciani L;Krylova O;Smalley MJ;Dale TC;Salinas PC
通讯作者：
Salinas PC
影响因子：
16.2
作者：
Crump, JG;Zhen, M;Bargmann, CI
通讯作者：
Bargmann, CI
DOI：
10.1073/pnas.0701140104
发表时间：
2007-03-13
影响因子：
11.1
作者：
Burkard, Mark E.;Randall, Catherine L.;Jallepalli, Prasad V.
通讯作者：
Jallepalli, Prasad V.
影响因子：
25
作者：
Godenschwege, TA;Hu, HL;Murphey, RK
通讯作者：
Murphey, RK
影响因子：
16.2
作者：
ISHII, N;WADSWORTH, WG;HEDGECOCK, EM
通讯作者：
HEDGECOCK, EM