Khare N, Baumgartner S
Department of Cell and Molecular Biology, Box 94, Lund University, S-22100, Lund, Sweden.
Mech Dev. 2000 Dec;99(1-2):199-202. doi: 10.1016/s0925-4773(00)00502-5.
Proteoglycans, the molecules of extracellular matrix, carry a highly negative charge due to their glycosaminoglycan (GAG) chains and large volumes. They were considered to play a secondary role in activities like cell division, adhesion, blood coagulation, etc. until the importance of their sugar chains in the fibroblast growth factor (FGF) signalling was discovered (Science 252 (1991) 1705; Cell 64 (1991) 841). Studies of mutations in the genes sugarless(sgl) and sulfateless (sfl) have proved that the proteoglycans involved in Wg signalling contain heparan sulfate GAG chains (Development 124 (1997) 2623; Development 124 (1997) 3055; Development 124 (1997) 3565; Development 126 (1999) 3715). This has led to the attribution of specific functions to these molecules (J. Cell Biol. 148 (2000) 227). The Glypican family of heparan sulfate proteoglycans (HSPGs) is characterized by core proteins with conserved cysteine residues and attachment to the cell surface by a glycosylphosphatidyl inositol (GPI) anchor. This may lead to endocytic pathways that are different from other HSPGs, higher lateral mobility and possible apical localisation in a cell (Proc. Natl. Acad. Sci, USA 85 (1988) 9557). Variations in their HS contents may effect binding properties and localisation (J. Cell Biol. 124 (1994) 149; J. Cell Biol. 132 (1996) 487), thus specialising each member for a unique biological function. Glypicans play important roles in morphogenetic pathways, e.g. human glypican 3 (GPC3) is mutated in Simpson-Golabi-Behmel syndrome making an individual prone to tumours (Nat. Genet. 12 (1996) 241). Dally, the first Drosophila member of the family, is essential for the wingless and decapentaplegic signalling pathways (Development 121 (1995) 3687; Development 124 (1997) 4113). Here, we report a new Drosophila glypican, dally-like protein (dlp) with all the features of a glypican. Based on expression studies we report its colocalisation with Wg.
蛋白聚糖是细胞外基质分子，由于其糖胺聚糖（GAG）链和较大体积而带有高度负电荷。在发现其糖链在成纤维细胞生长因子（FGF）信号传导中的重要性之前（《科学》252卷（1991年）第1705页；《细胞》64卷（1991年）第841页），它们被认为在细胞分裂、黏附、血液凝固等活动中起次要作用。对无糖（sgl）和无硫酸酯（sfl）基因中的突变研究证明，参与Wg信号传导的蛋白聚糖含有硫酸乙酰肝素GAG链（《发育》124卷（1997年）第2623页；《发育》124卷（1997年）第3055页；《发育》124卷（1997年）第3565页；《发育》126卷（1999年）第3715页）。这使得人们赋予这些分子特定功能（《细胞生物学杂志》148卷（2000年）第227页）。硫酸乙酰肝素蛋白聚糖（HSPG）的Glypican家族的特征是具有保守半胱氨酸残基的核心蛋白，并通过糖基磷脂酰肌醇（GPI）锚定附着在细胞表面。这可能导致不同于其他HSPG的内吞途径、更高的侧向流动性以及在细胞中可能的顶端定位（《美国国家科学院院刊》85卷（1988年）第9557页）。其硫酸乙酰肝素（HS）含量的变化可能影响结合特性和定位（《细胞生物学杂志》124卷（1994年）第149页；《细胞生物学杂志》132卷（1996年）第487页），从而使每个成员具有独特的生物学功能。Glypicans在形态发生途径中起重要作用，例如人类Glypican 3（GPC3）在辛普森 - 戈拉比 - 贝梅尔综合征中发生突变，使个体易患肿瘤（《自然遗传学》12卷（1996年）第241页）。该家族的第一个果蝇成员Dally对于无翅和Dpp信号传导途径至关重要（《发育》121卷（1995年）第3687页；《发育》124卷（1997年）第4113页）。在此，我们报道了一种新的果蝇Glypican，即类Dally蛋白（dlp），它具有Glypican的所有特征。基于表达研究，我们报道了它与Wg的共定位。
