A Role for the Juxtamembrane Domain of β-Dystroglycan in Agrin-Induced Acetylcholine Receptor Clustering
A Role for the Juxtamembrane Domain of β-Dystroglycan in Agrin-Induced Acetylcholine Receptor Clustering
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β-肌营养不良聚糖近膜结构域在集聚蛋白诱导的乙酰胆碱受体聚集中的作用
DOI：
10.1523/jneurosci.23-02-00392.2003
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
J. Campanelli
中科院分区：
文献类型：
--
作者：
J. Kahl;J. Campanelli
突触分化是发育过程中突触伴侣间信息分子交换的结果。在脊椎动物神经肌肉连接处，agrin是突触前运动神经元呈现的一种分子，对肌肉细胞的突触后分化起指导作用，最显著的是乙酰胆碱受体（achr）的聚集。虽然agrin是表征最好的突触原分子，但其作用机制尚不确定，但很明显，它需要受体酪氨酸激酶MuSK（肌肉特异性激酶）、细胞内蛋白rapsyn（一种src样激酶）和细胞骨架组分。此外，跨膜蛋白糖酐与细胞骨架相互作用，并与agrin反应性有关。该α -β异二聚体可通过胞外α亚基结合agrin，并通过β亚基与膜细胞骨架结合。在这项研究中，我们证明了在培养的肌肉细胞中过度表达糖酐的β亚基可以抑制agrin诱导的AChR聚集。缺失分析和点突变表明，这种抑制作用是由一个由碱性氨基酸组成的细胞内近膜区域介导的。最后，β-糖质失调介导的抑制作用扩展到AChR聚集所需的最小agrin片段，表明糖质失调在响应agrin的突触后分化中起重要作用。
Synaptic differentiation results from an exchange of informational molecules between synaptic partners during development. At the vertebrate neuromuscular junction, agrin is one molecule presented by the presynaptic motor neuron that plays an instructive role in postsynaptic differentiation of the muscle cell, most notably in aggregation of acetylcholine receptors (AChRs). Although agrin is the best-characterized synaptogenic molecule, its mechanism of action remains uncertain, but clearly, it requires the receptor tyrosine kinase MuSK (muscle-specific kinase), the intracellular protein rapsyn, an Src-like kinase, and cytoskeletal components. In addition, the transmembrane protein dystroglycan interacts with the cytoskeleton and is implicated in agrin responsiveness. This α–β heterodimer can bind agrin via its extracellular α subunit and associates with the membrane cytoskeleton via its β subunit. In this study, we demonstrate that overexpression of the β subunit of dystroglycan in cultured muscle cells inhibits agrin-induced AChR clustering. Deletion analysis and point mutagenesis demonstrate that the inhibition is mediated by an intracellular, juxtamembrane region composed of basic amino acids. Finally, the inhibition mediated by β-dystroglycan extends to the minimal agrin fragment required for AChR clustering, suggesting that dystroglycan plays an important role in postsynaptic differentiation in response to agrin.
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影响因子：
3.4
作者：
BenTal, N;Honig, B;McLaughlin, S
通讯作者：
McLaughlin, S
DOI：
10.1016/s0021-9258(18)43862-8
发表时间：
1994-12
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Philip A. Barker;G. Barbee;T. P. Misko;Eric M. Shooter
通讯作者：
Philip A. Barker;G. Barbee;T. P. Misko;Eric M. Shooter
影响因子：
3.3
作者：
Jha, Smita;Xu, Kaiping;Hoch, Werner
通讯作者：
Hoch, Werner
影响因子：
4.4
作者：
Zhang, WG;Irvin, BJ;Samelson, LE
通讯作者：
Samelson, LE