Differential targeting of components of the dystrophin complex to the postsynaptic membrane

Differential targeting of components of the dystrophin complex to the postsynaptic membrane
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抗肌营养不良蛋白复合物成分对突触后膜的差异靶向

DOI:
--
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发表时间:
2001
影响因子:
3.4
通讯作者:
J. Cartaud
J. Cartaud
中科院分区:
医学3区
文献类型:
--
作者:
S. Marchand;F. Stetzkowski;J. Cartaud

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越来越多的证据表明,肌营养不良蛋白聚糖参与了神经肌肉接头处烟碱乙酰胆碱受体的聚集[Littéet al.(1999)Nature Genet.,3,338-342]。肌营养不良聚糖是多分子复合物的一部分,在肌膜处与肌营养不良蛋白(肌营养不良蛋白相关蛋白复合物)相关,或在神经肌肉接头处与肌营养不良蛋白(肌营养不良蛋白相关蛋白复合物)相关。了解该复合物在发育中的突触中的组装使我们在电鳐电细胞中研究了其几种组分的细胞内路由和靶向,包括肌营养不良蛋白聚糖、突触营养蛋白、肌营养不良蛋白和小肌营养不良蛋白。我们先前证明,乙酰胆碱受体和rapsyn(突触处的43-kDa受体相关蛋白)通过胞吐途径共同靶向突触后膜[Marchand et al.(2000)神经科学杂志,20,521-528]。利用细胞分级分离、免疫纯化和免疫电镜技术,我们发现β-肌营养不良蛋白聚糖(一种组成位于神经支配膜的肌营养不良蛋白相关蛋白复合物核心的完整糖蛋白)与乙酰胆碱受体和rapsyn一起在高尔基体后囊泡中转运至突触后膜。 Syntrophin,复合物的外周细胞质蛋白,最初与这些胞吐囊泡。相反,这些高尔基体后囊泡中不存在抗肌萎缩蛋白和短肌萎缩蛋白,并直接与突触后膜相关。这项研究为肌营养不良蛋白相关蛋白复合物的各种组分的单独靶向和突触后膜上的逐步组装提供了第一个证据。
Accumulating evidence points to the participation of dystroglycan in the clustering of nicotinic acetylcholine receptors at the neuromuscular junction [Côtéet al.. (1999) Nature Genet., 3, 338–342]. Dystroglycan is part of a multimolecular complex, either associated with dystrophin (the dystrophin‐associated protein complex) at the sarcolemma or with utrophin (the utrophin‐associated protein complex) at the neuromuscular junction. Understanding the assembly of this complex at the developing synapse led us to investigate, in Torpedo electrocyte, the intracellular routing and the targeting of several of its components, including dystroglycan, syntrophin, dystrophin and dystrobrevin. We previously demonstrated that acetylcholine receptors and rapsyn, the 43‐kDa receptor‐associated protein at the synapse, are cotargeted to the postsynaptic membrane via the exocytic pathway [Marchand et al.. (2000) J. Neurosci., 20, 521–528]. Using cell fractionation, immunopurification and immuno‐electron microscope techniques, we show that β‐dystroglycan, an integral glycoprotein that constitutes the core of the dystrophin‐associated protein complex localized at the innervated membrane, is transported together with acetylcholine receptor and rapsyn in post‐Golgi vesicles en route to the postsynaptic membrane. Syntrophin, a peripheral cytoplasmic protein of the complex, associates initially with these exocytic vesicles. Conversely, dystrophin and dystrobrevin were absent from these post‐Golgi vesicles and associate directly with the postsynaptic membrane. This study provides the first evidence for a separate targeting of the various components of the dystrophin‐associated protein complex and a step‐by‐step assembly at the postsynaptic membrane.
加州鱼雷电器官中的肌营养不良蛋白与人体肌肉中的肌营养不良蛋白同源。
DOI: --
发表时间: 1989
期刊: The Journal of biological chemistry
影响因子: --
作者:
Chang,HW;Bock,E;Bonilla,E
通讯作者: Bonilla,E
电组织的 Mr 58,000 突触后蛋白与鱼雷肌营养不良蛋白和 Mr 87,000 突触后蛋白的关联。
DOI: --
发表时间: 1992
期刊: The Journal of biological chemistry
影响因子: --
作者:
Butler,MH;Douville,K;Murnane,AA;Kramarcy,NR;Cohen,JB;Sealock,R;Froehner,SC
通讯作者: Froehner,SC