Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Higashihiroshima, Hiroshima, Japan.
Connect Tissue Res. 2010 Oct;51(5):388-96. doi: 10.3109/03008200903537097.
Inherited deficiency for arylsulfatase (Ars) leads to lysosomal storage of sulfated compounds and to serious diseases such as growth retardation, heart failure, and demyelination in the central nervous system. Ars has been regarded as a lysosomal enzyme because of its hydrolytic activity on synthetic aromatic substrates and the lysosomal localization of its enzymatic activity. We previously demonstrated that a large portion of the mammalian arylsulfatase A (ArsA) protein exists on the cell surface of vascular endothelial cells, suggesting that ArsA plays a role in the components of the extracellular matrix. Here we show that ArsA functions as a substrate on which cells adhere and form protrusions. Coating culture plates with recombinant mouse ArsA (rmArsA) stimulates adhesion of human microvascular endothelial cells to the plate followed by the formation of cell protrusions as well as lamellipodia. rmArsA affects the architecture of the cytoskeleton, with a high density of actin filaments localized to peripheral regions of the cells and the extension of bundles of microtubules into the tips of cellular protrusions. rmArsA also affects the distribution pattern of the cell adhesion-associated proteins, integrin α2β1, and paxillin. rmArsA seems to modulate signaling of basic fibroblast growth factor (bFGF) stimulating cytoskeletal rearrangement. We also show that rmArsA tightly binds to sulfated polysaccharides. We suggest that mammalian ArsA plays a role as a novel component of the extracellular matrix. This viewpoint of Ars could be very useful for clarifying the mechanisms underpinning syndromes caused by the deficiency of the function of Ars genes.
遗传性芳基硫酸酯酶（Ars）缺乏会导致硫酸化化合物在溶酶体中积累，从而导致生长迟缓、心力衰竭和中枢神经系统脱髓鞘等严重疾病。由于其对合成芳香族底物的水解活性以及酶活性的溶酶体定位，Ars 一直被认为是一种溶酶体酶。我们之前证明，哺乳动物芳基硫酸酯酶 A（ArsA）的很大一部分存在于血管内皮细胞的细胞表面，这表明 ArsA 在细胞外基质的成分中发挥作用。在这里，我们表明 ArsA 作为细胞附着和形成突起的底物发挥作用。用重组小鼠 ArsA（rmArsA）包被培养板可刺激人微血管内皮细胞黏附到板上，随后形成细胞突起和片状伪足。rmArsA 影响细胞骨架的结构，细胞周围区域有高密度的肌动蛋白丝，微管束延伸到细胞突起的尖端。rmArsA 还影响细胞黏附相关蛋白整合素 α2β1 和桩蛋白的分布模式。rmArsA 似乎调节碱性成纤维细胞生长因子（bFGF）刺激细胞骨架重排的信号。我们还表明 rmArsA 与硫酸化多糖紧密结合。我们认为哺乳动物 ArsA 作为细胞外基质的一个新成分发挥作用。这种 Ars 的观点对于阐明 Ars 基因功能缺陷引起的综合征的机制非常有用。
