糖基化缺陷型Large（myd）小鼠神经肌肉接头的异常发育
Aberrant development of neuromuscular junctions in glycosylation-defective Large(myd) mice.
作者信息
Herbst Ruth, Iskratsch Thomas, Unger Ewald, Bittner Reginald E
机构信息
Center for Brain Research, Medical University of Vienna, Vienna, Austria.
出版信息
Neuromuscul Disord. 2009 May;19(5):366-78. doi: 10.1016/j.nmd.2009.02.011. Epub 2009 Apr 5.
Abstract
Mice deficient in the glycosyltransferase Large are characterized by severe muscle and central nervous system abnormalities. In this study, we show that the formation and maintenance of neuromuscular junctions in Large(myd) mice are greatly compromised. Neuromuscular junctions are not confined to the muscle endplate zone but are widely spread and are frequently accompanied by exuberant nerve sprouting. Nerve terminals are highly fragmented and binding of alpha-bungarotoxin to postsynaptic acetylcholine receptors (AChRs) is greatly reduced. In vitro, Large(myd) myotubes are responsive to agrin but produce aberrant AChR clusters, which are larger in area and less densely packed with AChRs. In addition, AChR expression on the cell surface is diminished suggesting that AChR assembly or transport is defective. These results together with the finding that O-linked glycosylation at neuromuscular junctions of Large(myd) mice is compromised indicate that the action of Large is necessary for proper neuromuscular junction development.
摘要
缺乏糖基转移酶Large的小鼠表现出严重的肌肉和中枢神经系统异常。在本研究中，我们发现Large(myd)小鼠神经肌肉接头的形成和维持受到极大损害。神经肌肉接头不限于肌肉终板区，而是广泛分布，并经常伴有旺盛的神经芽生。神经末梢高度碎片化，α-银环蛇毒素与突触后乙酰胆碱受体（AChRs）的结合大大减少。在体外，Large(myd)肌管对聚集蛋白有反应，但产生异常的AChR簇，其面积更大且AChRs的密集程度更低。此外，细胞表面的AChR表达减少，表明AChR组装或运输存在缺陷。这些结果以及Large(myd)小鼠神经肌肉接头处O-连接糖基化受损的发现表明，Large的作用对于神经肌肉接头的正常发育是必需的。
相似文献
1
Aberrant development of neuromuscular junctions in glycosylation-defective Large(myd) mice.糖基化缺陷型Large（myd）小鼠神经肌肉接头的异常发育
Neuromuscul Disord. 2009 May;19(5):366-78. doi: 10.1016/j.nmd.2009.02.011. Epub 2009 Apr 5.
2
Neural agrin increases postsynaptic ACh receptor packing by elevating rapsyn protein at the mouse neuromuscular synapse.神经聚集蛋白通过提高小鼠神经肌肉突触处的rapsyn蛋白水平，增加突触后乙酰胆碱受体的聚集。
Dev Neurobiol. 2008 Aug;68(9):1153-69. doi: 10.1002/dneu.20654.
3
Tyrosine phosphatases such as SHP-2 act in a balance with Src-family kinases in stabilization of postsynaptic clusters of acetylcholine receptors.酪氨酸磷酸酶（如SHP-2）在与Src家族激酶的平衡中发挥作用，以稳定乙酰胆碱受体的突触后簇。
BMC Neurosci. 2007 Jul 2;8:46. doi: 10.1186/1471-2202-8-46.
4
Synergistic effects of neuregulin and agrin on muscle acetylcholine receptor expression.神经调节蛋白与聚集蛋白对肌肉乙酰胆碱受体表达的协同作用。
Mol Cell Neurosci. 2004 Aug;26(4):558-69. doi: 10.1016/j.mcn.2004.04.009.
5
Muscle-specific expression of LARGE restores neuromuscular transmission deficits in dystrophic LARGE(myd) mice.肌肉特异性表达 LARGE 可恢复肌营养不良 LARGE(myd)小鼠的神经肌肉传递缺陷。
Hum Mol Genet. 2013 Feb 15;22(4):757-68. doi: 10.1093/hmg/dds483. Epub 2012 Dec 6.
6
Expression of Nav1.6 sodium channels by Schwann cells at neuromuscular junctions: role in the motor endplate disease phenotype.施万细胞在神经肌肉接头处表达Nav1.6钠通道：在运动终板疾病表型中的作用。
Glia. 2006 Jan 1;53(1):13-23. doi: 10.1002/glia.20252.
7
Abnormalities in neuromuscular junction structure and skeletal muscle function in mice lacking the P2X2 nucleotide receptor.缺乏P2X2核苷酸受体的小鼠神经肌肉接头结构和骨骼肌功能异常。
Neuroscience. 2007 Sep 7;148(3):700-11. doi: 10.1016/j.neuroscience.2007.06.050. Epub 2007 Jul 17.
8
Acetylcholine receptor organization at the dystrophic extraocular muscle neuromuscular junction.营养不良性眼外肌神经肌肉接头处的乙酰胆碱受体组织
Anat Rec (Hoboken). 2007 Jul;290(7):846-54. doi: 10.1002/ar.20525.
9
Defective neuromuscular synaptogenesis in agrin-deficient mutant mice.聚集蛋白缺陷型突变小鼠中神经肌肉突触发生缺陷
Cell. 1996 May 17;85(4):525-35. doi: 10.1016/s0092-8674(00)81253-2.
10
Disruption of the mouse Large gene in the enr and myd mutants results in nerve, muscle, and neuromuscular junction defects.在enr和myd突变体中破坏小鼠Large基因会导致神经、肌肉和神经肌肉接头缺陷。
Mol Cell Neurosci. 2005 Apr;28(4):757-69. doi: 10.1016/j.mcn.2004.12.007.
引用本文的文献
1
Dystroglycanopathy: From Elucidation of Molecular and Pathological Mechanisms to Development of Treatment Methods.肌营养不良糖蛋白病：从分子和病理机制阐明到治疗方法的发展。
Int J Mol Sci. 2021 Dec 6;22(23):13162. doi: 10.3390/ijms222313162.
2
RNA Targeting in Inherited Neuromuscular Disorders: Novel Therapeutic Strategies to Counteract Mis-Splicing.遗传性神经肌肉疾病中的 RNA 靶向：纠正剪接错误的新型治疗策略。
Cells. 2021 Oct 22;10(11):2850. doi: 10.3390/cells10112850.
3
The Neuromuscular Junction: Roles in Aging and Neuromuscular Disease.神经肌肉接头：在衰老和神经肌肉疾病中的作用。
Int J Mol Sci. 2021 Jul 28;22(15):8058. doi: 10.3390/ijms22158058.
4
Alterations of neuromuscular junctions in Duchenne muscular dystrophy.Duchenne 型肌营养不良症中的神经肌肉接头改变。
Neurosci Lett. 2020 Oct 15;737:135304. doi: 10.1016/j.neulet.2020.135304. Epub 2020 Aug 17.
5
NAD+ improves neuromuscular development in a zebrafish model of FKRP-associated dystroglycanopathy.NAD+ 改善 FKRP 相关的聚糖蛋白病斑马鱼模型中的神经肌肉发育。
Skelet Muscle. 2019 Aug 7;9(1):21. doi: 10.1186/s13395-019-0206-1.
6
The roles of dystroglycan in the nervous system: insights from animal models of muscular dystrophy.肌营养不良症动物模型研究揭示了 dystroglycan 在神经系统中的作用。
Dis Model Mech. 2018 Dec 19;11(12):dmm035931. doi: 10.1242/dmm.035931.
7
Autologous intramuscular transplantation of engineered satellite cells induces exosome-mediated systemic expression of Fukutin-related protein and rescues disease phenotype in a murine model of limb-girdle muscular dystrophy type 2I.工程化卫星细胞的自体肌肉内移植诱导外泌体介导的福库汀相关蛋白的全身表达，并在2I型肢带型肌营养不良小鼠模型中挽救疾病表型。
Hum Mol Genet. 2017 Oct 1;26(19):3682-3698. doi: 10.1093/hmg/ddx252.
8
Clinical, pathologic, and mutational spectrum of dystroglycanopathy caused by LARGE mutations.由 LARGE 基因突变引起的 dystroglycanopathy 的临床、病理和突变谱。
J Neuropathol Exp Neurol. 2014 May;73(5):425-41. doi: 10.1097/NEN.0000000000000065.
9
CLP1 links tRNA metabolism to progressive motor-neuron loss.CLP1 将 tRNA 代谢与进行性运动神经元丧失联系起来。
Nature. 2013 Mar 28;495(7442):474-80. doi: 10.1038/nature11923. Epub 2013 Mar 10.
10
Muscle-specific expression of LARGE restores neuromuscular transmission deficits in dystrophic LARGE(myd) mice.肌肉特异性表达 LARGE 可恢复肌营养不良 LARGE(myd)小鼠的神经肌肉传递缺陷。
Hum Mol Genet. 2013 Feb 15;22(4):757-68. doi: 10.1093/hmg/dds483. Epub 2012 Dec 6.
本文引用的文献
1
A histochemical method for localizing cholinesterase activity.一种用于定位胆碱酯酶活性的组织化学方法。
Proc Soc Exp Biol Med. 1949 Apr;70(4):617-22. doi: 10.3181/00379727-70-17013.
2
Structural factors influencing the efficacy of neuromuscular transmission.影响神经肌肉传递效能的结构因素。
Ann N Y Acad Sci. 2008;1132:1-12. doi: 10.1196/annals.1405.003. Epub 2007 Dec 20.
3
Aberrant neuromuscular junctions and delayed terminal muscle fiber maturation in alpha-dystroglycanopathies.α-肌营养不良糖蛋白病中的异常神经肌肉接头和终末肌纤维成熟延迟
Hum Mol Genet. 2006 Apr 15;15(8):1279-89. doi: 10.1093/hmg/ddl045. Epub 2006 Mar 10.
4
Dystroglycan: from biosynthesis to pathogenesis of human disease.肌营养不良聚糖：从生物合成到人类疾病的发病机制
J Cell Sci. 2006 Jan 15;119(Pt 2):199-207. doi: 10.1242/jcs.02814.
5
Ocular abnormalities in Large(myd) and Large(vls) mice, spontaneous models for muscle, eye, and brain diseases.大型（myd）和大型（vls）小鼠的眼部异常，肌肉、眼睛和脑部疾病的自发模型。
Mol Cell Neurosci. 2005 Oct;30(2):160-72. doi: 10.1016/j.mcn.2005.07.009.
6
Agrin promotes synaptic differentiation by counteracting an inhibitory effect of neurotransmitter.集聚蛋白通过抵消神经递质的抑制作用来促进突触分化。
Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11088-93. doi: 10.1073/pnas.0504806102. Epub 2005 Jul 25.
7
Neurotransmitter acetylcholine negatively regulates neuromuscular synapse formation by a Cdk5-dependent mechanism.神经递质乙酰胆碱通过一种依赖细胞周期蛋白依赖性激酶5（Cdk5）的机制对神经肌肉突触的形成起负向调节作用。
Neuron. 2005 May 19;46(4):569-79. doi: 10.1016/j.neuron.2005.04.002.
8
Disruption of the mouse Large gene in the enr and myd mutants results in nerve, muscle, and neuromuscular junction defects.在enr和myd突变体中破坏小鼠Large基因会导致神经、肌肉和神经肌肉接头缺陷。
Mol Cell Neurosci. 2005 Apr;28(4):757-69. doi: 10.1016/j.mcn.2004.12.007.
9
Structural abnormalities at neuromuscular synapses lacking multiple syntrophin isoforms.缺乏多种肌萎缩蛋白亚型的神经肌肉突触处的结构异常。
J Neurosci. 2004 Nov 17;24(46):10302-9. doi: 10.1523/JNEUROSCI.3408-04.2004.
10
LARGE can functionally bypass alpha-dystroglycan glycosylation defects in distinct congenital muscular dystrophies.LARGE可在不同的先天性肌营养不良中通过功能代偿α- dystroglycan糖基化缺陷。
Nat Med. 2004 Jul;10(7):696-703. doi: 10.1038/nm1059. Epub 2004 Jun 6.
Zotero 插件