MOLECULAR ANALYSIS OF CELL-SURFACE BETA-1,4-GALACTOSYLTRANSFERASE FUNCTION DURING CELL-MIGRATION
MOLECULAR ANALYSIS OF CELL-SURFACE BETA-1,4-GALACTOSYLTRANSFERASE FUNCTION DURING CELL-MIGRATION
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DOI：
10.1073/pnas.91.6.2095
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发表时间：
1994-03-15
影响因子：
11.1
通讯作者：
SHUR, BD
中科院分区：
文献类型：
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作者：
APPEDDU, PA;SHUR, BD
尽管细胞外基质的细胞表面受体的鉴定和表征，但它们的相对表达和细胞骨架缔合如何调节细胞迁移尚不清楚。先前的研究已经在迁移细胞表面发现了β-1，4-半乳糖基转移酶（GalTase; EC 2.4.1.38），它通过与细胞骨架结合并与层粘连蛋白E8结构域中的N-连接低聚糖结合来介导细胞在基底层基质上的迁移。在这项研究中，GalTase在细胞迁移过程中的功能进行了检查，直接通过分析稳定转染的细胞系的迁移率，其中表面GalTase的相对水平和它的能力与细胞骨架的改变。我们在这里表明，细胞骨架包含一个限制，饱和，表面GalTase结合位点的数量。此外，细胞迁移率与表面GalTase与细胞骨架结合的能力呈负相关。升高表面半乳糖苷酶超过细胞骨架结合位点的数量降低了细胞迁移的速率，而减少可用于结合细胞骨架的表面半乳糖苷酶的量增加了迁移速率。这些结果表明，基底层上的细胞迁移率是直接依赖于表面GalTase的表达和这种蛋白质的能力，以与有限数量的细胞色素结合位点。
Despite the identification and characterization of cell surface receptors for the extracellular matrix, it is unknown how their relative expression and cytoskeletal association regulate cell migration. Previous studies have identified beta-1,4-galactosyltransferase (GalTase; EC 2.4.1.38) on the surface of migrating cells, where it mediates cell migration on basal lamina matrices by associating with the cytoskeleton and binding to N-linked oligosaccharides in the E8 domain of laminin. In this study, the function of GalTase during cell migration was examined directly by analyzing the migration rate of stably transfected cell lines in which the relative level of surface GalTase and its ability to associate with the cytoskeleton were altered. We show here that the cytoskeleton contains a limiting, saturable, number of binding sites for surface GalTase. Furthermore, the rate of cell migration was inversely related to the ability of surface GalTase to associate with the cytoskeleton. Elevating surface GalTase in excess of the number of cytoskeleton-binding sites reduced the rate of cell migration, whereas decreasing the amount of surface GalTase available to bind the cytoskeleton increased migration rates. These results show that the rate of cell migration on basal lamina is directly dependent upon the expression of surface GalTase and the ability of this protein to associate with a limiting number of cytoskeleton-binding sites.