α3钠钾ATP酶是聚集蛋白的一种神经元受体。

Alpha3Na+/K+-ATPase is a neuronal receptor for agrin.

作者信息

Hilgenberg Lutz G W, Su Hailing, Gu Huaiyu, O'Dowd Diane K, Smith Martin A

机构信息

Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA 92697, USA.

出版信息

Cell. 2006 Apr 21;125(2):359-69. doi: 10.1016/j.cell.2006.01.052.

DOI:10.1016/j.cell.2006.01.052

PMID:16630822

Abstract

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 alpha3 subunit of the Na+/K+-ATPase (NKA) in CNS neurons. Colocalization with agrin binding sites at synapses supports the hypothesis that the alpha3NKA is a neuronal agrin receptor. Agrin inhibition of alpha3NKA 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 alpha3NKA function. These data demonstrate that, through its interaction with the alpha3NKA, agrin regulates activity-dependent processes in neurons, providing a molecular framework for agrin action in the CNS.

摘要

聚集蛋白通过与受体酪氨酸激酶MuSK相互作用，介导发育中的神经肌肉接头处乙酰胆碱受体（AChR）的聚集。聚集蛋白还参与大脑中的多种功能。然而，聚集蛋白在神经组织中发挥作用的机制尚不清楚。在此，我们提供生化证据表明，聚集蛋白与中枢神经系统（CNS）神经元中的Na+/K+-ATP酶（NKA）的α3亚基结合。与突触处聚集蛋白结合位点的共定位支持α3NKA是神经元聚集蛋白受体的假说。聚集蛋白对α3NKA活性的抑制导致培养的皮质神经元和急性切片中膜去极化和动作电位频率增加。一种作为竞争性拮抗剂的聚集蛋白片段可降低动作电位频率，表明内源性聚集蛋白调节天然α3NKA的功能。这些数据表明，聚集蛋白通过与α3NKA相互作用，调节神经元中依赖活动的过程，为聚集蛋白在中枢神经系统中的作用提供了分子框架。