Bergen Dylan J M, Stevenson Nicola L, Skinner Roderick E H, Stephens David J, Hammond Christina L
Cell Biology Laboratories, School of Biochemistry, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.
School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.
Biol Open. 2017 Aug 15;6(8):1180-1189. doi: 10.1242/bio.025502.
The Golgi is essential for glycosylation of newly synthesised proteins including almost all cell-surface and extracellular matrix proteoglycans. Giantin, encoded by the gene, is a member of the golgin family of proteins that reside within the Golgi stack, but its function remains elusive. Loss of function of giantin in rats causes osteochondrodysplasia; knockout mice show milder defects, notably a cleft palate. , giantin has been implicated in Golgi organisation, biosynthetic trafficking, and ciliogenesis. Here we show that loss of function of giantin in zebrafish, using either morpholino or knockout techniques, causes defects in cilia function. Giantin morphants have fewer cilia in the neural tube and those remaining are longer. Mutants have the same number of cilia in the neural tube but these cilia are also elongated. Scanning electron microscopy shows that loss of giantin results in an accumulation of material at the ciliary tip, consistent with a loss of function of retrograde intraflagellar transport. Mutants show milder defects than morphants consistent with adaptation to loss of giantin.
高尔基体对于新合成蛋白质的糖基化至关重要，这些蛋白质包括几乎所有细胞表面和细胞外基质蛋白聚糖。由该基因编码的巨蛋白是驻留在高尔基体堆栈中的高尔基体蛋白家族的成员，但其功能仍然难以捉摸。大鼠中巨蛋白功能丧失会导致骨软骨发育不良；基因敲除小鼠表现出较轻微的缺陷，尤其是腭裂。因此，巨蛋白与高尔基体组织、生物合成运输和纤毛发生有关。在这里我们表明，使用吗啉代或基因敲除技术在斑马鱼中使巨蛋白功能丧失会导致纤毛功能缺陷。巨蛋白 morphant 在神经管中的纤毛较少，而剩余的纤毛较长。突变体在神经管中的纤毛数量相同，但这些纤毛也伸长了。扫描电子显微镜显示，巨蛋白的缺失导致纤毛尖端物质积累，这与逆向鞭毛内运输功能丧失一致。与适应巨蛋白缺失一致，突变体表现出比 morphant 更轻微的缺陷。
