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首页> 外文期刊>Cell Reports >Retinal Proteoglycans Act as Cellular Receptors for Basement Membrane Assembly to Control Astrocyte Migration and Angiogenesis
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Retinal Proteoglycans Act as Cellular Receptors for Basement Membrane Assembly to Control Astrocyte Migration and Angiogenesis

机译：视网膜蛋白聚糖充当基底膜组装的细胞受体，以控制星形胶质细胞的迁移和血管生成。

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The basement membrane is crucial for cell polarity, adhesion, and motility, but how it is assembled on the 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.
机译：基底膜对于细胞的极性，粘附和运动至关重要，但是如何在细胞表面组装仍然不清楚。在这里，我们发现在神经视网膜中蛋白聚糖的糖胺聚糖（GAG）侧链的消融破坏了视网膜基底膜，导致星形胶质细胞迁移和血管生成减少。使用遗传删除和延时成像，我们显示视网膜星形胶质细胞需要神经源性PDGF作为化学引诱信号，而视网膜基底膜则作为迁移基质。硫酸乙酰肝素的遗传切除不会产生与GAG空突变体相同的缺陷。相反，酶促除去硫酸乙酰肝素和硫酸软骨素一起抑制了从头层粘连蛋白网络的组装。这些结果表明乙酰肝素和硫酸软骨素蛋白聚糖均参与视网膜基底膜的组装，从而促进星形胶质细胞的迁移和血管生成。

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