The dystroglycan complex is necessary for stabilization of acetylcholine receptor clusters at neuromuscular junctions and formation of the synaptic basement membrane.
The dystroglycan complex is necessary for stabilization of acetylcholine receptor clusters at neuromuscular junctions and formation of the synaptic basement membrane.
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DOI：
10.1083/jcb.152.3.435
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发表时间：
2001-02-05
期刊：
影响因子：
--
通讯作者：
Carbonetto S
中科院分区：
文献类型：
--
作者：
Jacobson C;Côté PD;Rossi SG;Rotundo RL;Carbonetto S
肌营养不良蛋白相关蛋白（DAP）复合物跨越肌膜膜，将细胞骨架与每根肌纤维周围的基底膜连接起来。先前已将 DAP 复合体的缺陷与多种肌营养不良症联系起来。其他证据表明 DAP 复合物在神经肌肉突触的形成中发挥作用。我们发现，从dystroglycan−/−胚胎干细胞分化而来的肌管对集聚蛋白有反应，但产生的乙酰胆碱受体（AChR）簇的面积比dystroglycan+/+肌管大两到三倍，密度约为其一半，并且稳定性明显低于dystroglycan+/+肌管。在缺乏肌营养不良的嵌合小鼠中，神经肌肉接头处的 AChR 也受到类似的影响，并且这些接头处的神经末梢尺寸也有协调增加。在培养物和体内，肌营养不良聚糖的缺失会破坏层粘连蛋白、基底膜聚糖和乙酰胆碱酯酶 (AChE) 的 AChR 簇的定位，但不会破坏 rapsyn 或 agrin 的定位。用层粘连蛋白处理培养物中的肌管会在肌营养不良聚糖+/+上诱导AChR簇，但不会在−/−肌管上诱导AChR簇。这些结果表明，肌营养不良聚糖对于突触基底膜的组装至关重要，最显着的是通过其与基底膜聚糖的结合来定位 AChE。此外，他们认为肌营养不良聚糖在 AChR 簇的组织和稳定中发挥作用，这似乎是通过其与层粘连蛋白的结合介导的。
The dystrophin-associated protein (DAP) complex spans the sarcolemmal membrane linking the cytoskeleton to the basement membrane surrounding each myofiber. Defects in the DAP complex have been linked previously to a variety of muscular dystrophies. Other evidence points to a role for the DAP complex in formation of nerve–muscle synapses. We show that myotubes differentiated from dystroglycan−/− embryonic stem cells are responsive to agrin, but produce acetylcholine receptor (AChR) clusters which are two to three times larger in area, about half as dense, and significantly less stable than those on dystroglycan+/+ myotubes. AChRs at neuromuscular junctions are similarly affected in dystroglycan-deficient chimeric mice and there is a coordinate increase in nerve terminal size at these junctions. In culture and in vivo the absence of dystroglycan disrupts the localization to AChR clusters of laminin, perlecan, and acetylcholinesterase (AChE), but not rapsyn or agrin. Treatment of myotubes in culture with laminin induces AChR clusters on dystroglycan+/+, but not −/− myotubes. These results suggest that dystroglycan is essential for the assembly of a synaptic basement membrane, most notably by localizing AChE through its binding to perlecan. In addition, they suggest that dystroglycan functions in the organization and stabilization of AChR clusters, which appear to be mediated through its binding of laminin.
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影响因子：
5.5
作者：
ANDERSON, MJ;COHEN, MW
通讯作者：
COHEN, MW
DOI：
10.1073/pnas.78.8.5230
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
FROEHNER, SC;GULBRANDSEN, V;COHEN, JB
通讯作者：
COHEN, JB
影响因子：
7.8
作者：
ANDERSON, MJ
通讯作者：
ANDERSON, MJ
层粘连蛋白聚合诱导受体细胞骨架网络。
影响因子：
7.8
作者：
Colognato, H;Winkelmann, D A;Yurchenco, P D
通讯作者：
Yurchenco, P D
DOI：
10.1073/pnas.87.9.3264
发表时间：
1990-05-01
影响因子：
11.1
作者：
EHRIG, K;LEIVO, I;ENGVALL, E
通讯作者：
ENGVALL, E