a3Na+/K+-ATPase is a neuronal receptor for Agrin
a3Na+/K+-ATPase is a neuronal receptor for Agrin
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DOI：
10.1016/j.cell.2006.01.052
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发表时间：
2006-04-21
期刊：
影响因子：
64.5
通讯作者：
Smith, MA
中科院分区：
文献类型：
--
作者：
Hilgenberg, LGW;Su, HL;Smith, MA
Agrin通过与受体酪氨酸激酶MuSK的相互作用，在发育中的神经肌肉连接处介导乙酰胆碱受体（AChR）的积累。Agrin还与大脑的一些功能有关。然而，agrin在神经组织中发挥作用的机制尚不清楚。在这里，我们提出了生化证据表明，在中枢神经系统神经元中，agrin与Na+/K+- atp酶（NKA）的α 3亚基结合。与突触上的agrin结合位点的共定位支持了alpha 3NKA是神经元的agrin受体的假设。agin抑制α 3NKA活性导致培养和急性切片皮层神经元膜去极化和动作电位频率增加。作为竞争性拮抗剂的agrin片段可抑制动作电位频率，表明内源性agrin调节天然α 3NKA功能。这些数据表明，通过与α 3NKA的相互作用，agrin调节神经元的活动依赖过程，为agrin在中枢神经系统中的作用提供了分子框架。
Agrin, through its interaction with the receptor tyrosine kinase MuSK, mediates accumulation of acetylcholine receptors (AChR) at the developing neuromuscular junction. Agrin has also been implicated in several functions in brain. However, the mechanism by which agrin exerts its effects in neural tissue is unknown. Here we present biochemical evidence that agrin binds to the alpha 3 subunit of the Na+/K+-ATPase (NKA) in CNS neurons. Colocalization with agrin binding sites at synapses supports the hypothesis that the alpha 3NKA is a neuronal agrin receptor. Agrin inhibition of alpha 3NKA activity results in membrane depolarization and increased action potential frequency in cortical neurons in culture and acute slice. An agrin fragment that acts as a competitive antagonist depresses action potential frequency, showing that endogenous agrin regulates native alpha 3NKA function. These data demonstrate that, through its interaction with the alpha 3NKA, agrin regulates activity-dependent processes in neurons, providing a molecular framework for agrin action in the CNS.