Retinal Proteoglycans Act as Cellular Receptors for Basement Membrane Assembly to Control Astrocyte Migration and Angiogenesis.
Retinal Proteoglycans Act as Cellular Receptors for Basement Membrane Assembly to Control Astrocyte Migration and Angiogenesis.
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DOI：
10.1016/j.celrep.2016.10.035
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发表时间：
2016-11-08
期刊：
影响因子：
8.8
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Tao C;Zhang X
基底膜对细胞极性、粘附和运动性至关重要，但它如何在细胞表面组装仍不清楚。在这里，我们发现消融神经视网膜中蛋白多糖的糖胺聚糖（GAG）侧链破坏了视网膜基底膜，导致星形胶质细胞迁移受阻和血管生成减少。使用基因缺失和延时成像，我们表明，视网膜星形胶质细胞需要神经源性PDGF作为化学吸引线索和视网膜基底膜作为迁移基板。硫酸乙酰肝素的基因消融不会产生与GAG无效突变体相同的缺陷。相反，硫酸乙酰肝素和硫酸软骨素的酶促去除一起抑制从头层粘连蛋白网络组装。这些结果表明，乙酰肝素和硫酸软骨素蛋白聚糖参与视网膜基底膜组装，从而促进星形胶质细胞迁移和血管生成。
The basement membrane is crucial for cell polarity, adhesion and motility, but how it is assembled on cell surface remains unclear. Here, we find that ablation of glycosaminoglycan (GAG) side chains of proteoglycans in the neuroretina disrupts the retinal basement membrane, leading to arrested astrocyte migration and reduced angiogenesis. Using genetic deletion and time-lapse imaging, we show that retinal astrocytes require neuronal-derived PDGF as a chemoattractive cue and the retinal basement membrane as a migratory substrate. Genetic ablation of heparan sulfates does not produce the same defects as GAG null mutants. In contrast, enzymatic removal of heparan sulfates and chondroitin sulfates together inhibits de novo laminin network assembly. These results indicate that both heparan and chondroitin sulfate proteoglycans participate in retinal basement membrane assembly, thus promoting astrocyte migration and angiogenesis.
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