Overexpression of the CT GalNAc transferase in skeletal muscle alters myofiber growth, neuromuscular structure, and laminin expression.
Overexpression of the CT GalNAc transferase in skeletal muscle alters myofiber growth, neuromuscular structure, and laminin expression.
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骨骼肌中 CT GalNAc 转移酶的过度表达会改变肌纤维生长、神经肌肉结构和层粘连蛋白表达。
DOI：
10.1006/dbio.2001.0530
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Martin,PaulT
中科院分区：
文献类型：
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作者：
Xia,Bing;Hoyte,Kwame;Kammesheidt,Anja;Deerinck,Tom;Ellisman,Mark;Martin,PaulT
碳水化合物已被证明介导或调节神经系统发育中的许多重要事件;然而，很少有证据表明它们直接参与突触的发育。在神经肌肉接头的突触发育中可能重要的一种碳水化合物结构是CT碳水化合物抗原{GalNAcβ 1，4 [NeuAcα 2，3]Galβ1（-3GalNAc或-4GlcNAc）}。CT抗原的突触定位是由于末端β 1，4 GalNAc连接的存在，并且这种连接在许多物种中定位于神经肌肉接头。在这里，我们表明，一种酶，可以创建突触CT结构，CT GalNAc转移酶，也仅限于小鼠的神经肌肉接头。使用转基因小鼠，我们表明，过度表达的CT GalNAc转移酶在突触外区域的骨骼肌纤维造成多达60%的成年肌纤维的直径减少和一个数量级的增加卫星细胞。转基因小鼠的神经肌肉接头的次级褶皱的数量严重减少，雪旺氏细胞的过程中存在的突触间隙，次级褶皱往往与活动区错位。此外，多个突触前专业化发生在个别肌纤维。此外，一些正常的突触蛋白，包括层粘连蛋白α4，层粘连蛋白α5，utrophin，和NCAM，表达沿着突触外区域的肌纤维。在转基因小鼠中，显示与CT抗原糖基化增加的肌肉蛋白之一是α-肌营养不良聚糖。这些实验提供了第一个体内证据，突触碳水化合物抗原在神经肌肉突触的发育中具有重要作用，并表明CT抗原参与控制突触分子的表达。
Carbohydrates have been shown to mediate or modulate a number of important events in the development of the nervous system; however, there is little evidence that they participate directly in the development of synapses. One carbohydrate structure that is likely to be important in synaptic development of the neuromuscular junction is the CT carbohydrate antigen {GalNAcβ1,4[NeuAcα2,3]Galβ1(-3GalNAc or -4GlcNAc)}. The synaptic localization of the CT antigen is due to the presence of the terminal β1,4 GalNAc linkage, and such linkages are localized to the neuromuscular junction in many species. Here we show that an enzyme that can create the synaptic CT structure, the CT GalNAc transferase, is also confined to the neuromuscular junction in mice. Using transgenic mice, we show that overexpression of the CT GalNAc transferase in extrasynaptic regions in skeletal myofibers caused as much as a 60% reduction in the diameter of adult myofibers and an order of magnitude increase in satellite cells. Neuromuscular junctions of transgenic mice had severely reduced numbers of secondary folds, Schwann cell processes were present in the synaptic cleft, and secondary folds were often misaligned with active zones. In addition, multiple presynaptic specializations occurred on individual myofibers. In addition, some normally synaptic proteins, including laminin α4, laminin α5, utrophin, and NCAM, were expressed along extrasynaptic regions of myofibers. One of the muscle proteins that displayed increased glycosylation with the CT antigen in the transgenic mice was α-dystroglycan. These experiments provide the first in vivo evidence that a synaptic carbohydrate antigen has important roles in the development of the neuromuscular synapse and suggest that the CT antigen is involved in controlling the expression of synaptic molecules.