Biochemical and biophysical changes underlie the mechanisms of basement membrane disruptions in a mouse model of dystroglycanopathy.
Biochemical and biophysical changes underlie the mechanisms of basement membrane disruptions in a mouse model of dystroglycanopathy.
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DOI：
10.1016/j.matbio.2013.02.002
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发表时间：
2013-04-24
期刊：
影响因子：
6.9
通讯作者：
Hu, Huaiyu
中科院分区：
文献类型：
--
作者：
Zhang, Peng;Yang, Yuan;Candiello, Joseph;Thorn, Trista L.;Gray, Noel;Halfter, Willi M.;Hu, Huaiyu
糖基转移酶如蛋白质O-甘露糖N-乙酰葡糖胺转移酶1（POMGnT 1）的突变会导致基底膜（BM）破裂，从而导致神经元异位和肌营养不良。虽然突变减少了肌营养不良聚糖介导的细胞-ECM相互作用，但BM破坏的原因和机制仍不清楚。在这项研究中，我们建立了一个体外模型来测量BM在神经干细胞表面的组装。与对照细胞相比，在POMGnT 1敲除的神经干细胞上的BM组装率显著降低。此外，免疫荧光染色和定量蛋白质组学分析的内界膜（ILM），BM的视网膜，揭示了层粘连蛋白-111和nidogen-1减少POMGnT 1基因敲除小鼠。最后，原子力显微镜显示，POMGnT 1基因敲除小鼠的ILM更薄，表面形貌发生了改变。综合结果表明，关键BM组分水平的降低导致POMGnT 1敲除小鼠的BM减弱的物理变化。这些变化是由神经组织发育扩张期间BM组装速率降低引起的。
Mutations in glycosyltransferases, such as protein O-mannose N-acetylglucosaminyltransferase 1 (POMGnT1), causes disruptions of basement membranes (BMs) that results in neuronal ectopias and muscular dystrophy. While the mutations diminish dystroglycan-mediated cell-ECM interactions, the cause and mechanism of BM disruptions remain unclear. In this study, we established an in vitro model to measure BM assembly on the surface of neural stem cells. Compared to control cells, the rate of BM assembly on POMGnT1 knockout neural stem cells was significantly reduced. Further, immunofluorescence staining and quantitative proteomic analysis of the inner limiting membrane (ILM), a BM of the retina, revealed that laminin-111 and nidogen-1 were reduced in POMGnT1 knockout mice. Finally, atomic force microscopy showed that the ILM from POMGnT1 knockout mice was thinner with an altered surface topography. The results combined demonstrate that reduced levels of key BM components cause physical changes that weaken the BM in POMGnT1 knockout mice. These changes are caused by a reduced rate of BM assembly during the developmental expansion of the neural tissue.
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DOI：
10.1083/jcb.122.4.809
发表时间：
1993-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ervasti JM;Campbell KP
通讯作者：
Campbell KP
影响因子：
4.8
作者：
Kanagawa, Motoi;Omori, Yoshihiro;Toda, Tatsushi
通讯作者：
Toda, Tatsushi
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
影响因子：
3.5
作者：
Brockington, M;Yuva, Y;Muntoni, F
通讯作者：
Muntoni, F
影响因子：
64.5
作者：
Henry, MD;Campbell, KP
通讯作者：
Campbell, KP