Fransson L-A, Belting M, Cheng F, Jönsson M, Mani K, Sandgren S
Department of Cell and Molecular Biology, Section for Cell and Matrix Biology, BMC C13, Lund University, 221 84 Lund, Sweden.
Cell Mol Life Sci. 2004 May;61(9):1016-24. doi: 10.1007/s00018-004-3445-0.
Mutations in glypican genes cause dysmorphic and overgrowth syndromes in men and mice, abnormal development in flies and worms, and defective gastrulation in zebrafish and ascidians. All glypican core proteins share a characteristic pattern of 14 conserved cysteine residues. Upstream from the C-terminal membrane anchorage are 3-4 heparan sulfate attachment sites. Cysteines in glypican-1 can become nitrosylated by nitric oxide in a copper-dependent reaction. When glypican-1 is exposed to ascorbate, nitric oxide is released and participates in deaminative cleavage of heparan sulfate at sites where the glucosamines have a free amino group. This process takes place while glypican-1 recycles via a nonclassical, caveolin-1-associated route. Glypicans are involved in growth factor signalling and transport, e.g. of polyamines. Cargo can be unloaded from heparan sulfate by nitric oxide-dependent degradation. How glypican and its degradation products and the cargo exit from the recycling route is an enigma.
磷脂酰肌醇蛋白聚糖基因的突变会导致人类和小鼠出现畸形和过度生长综合征，果蝇和线虫出现发育异常，斑马鱼和海鞘出现原肠胚形成缺陷。所有磷脂酰肌醇蛋白聚糖核心蛋白都具有由14个保守半胱氨酸残基组成的特征模式。在C端膜锚定上游有3 - 4个硫酸乙酰肝素附着位点。磷脂酰肌醇蛋白聚糖-1中的半胱氨酸可通过依赖铜的反应被一氧化氮亚硝基化。当磷脂酰肌醇蛋白聚糖-1暴露于抗坏血酸时，一氧化氮被释放，并参与硫酸乙酰肝素在葡糖胺具有游离氨基的位点的脱氨基裂解。这个过程发生在磷脂酰肌醇蛋白聚糖-1通过非经典的、与小窝蛋白-1相关的途径循环时。磷脂酰肌醇蛋白聚糖参与生长因子信号传导和运输，例如多胺的运输。货物可以通过一氧化氮依赖的降解从硫酸乙酰肝素上卸载。磷脂酰肌醇蛋白聚糖及其降解产物以及货物如何从循环途径中排出仍是一个谜。
