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PAPS 转运蛋白 PST-1 是硫酸乙酰肝素化所必需的,对秀丽隐杆线虫的生存和神经发育至关重要。

The PAPS transporter PST-1 is required for heparan sulfation and is essential for viability and neural development in C. elegans.

机构信息

Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

出版信息

J Cell Sci. 2009 Dec 15;122(Pt 24):4492-504. doi: 10.1242/jcs.050732. Epub 2009 Nov 17.

Abstract

Sulfations of sugars, such as heparan sulfates (HS), or tyrosines require the universal sulfate donor 3'-phospho-adenosine-5'-phosphosulfate (PAPS) to be transported from the cytosol into the Golgi. Metazoan genomes encode two putative PAPS transporters (PAPST1 and PAPST2), which have been shown in vitro to preferentially transport PAPS across membranes. We have identified the C. elegans orthologs of PAPST1 and PAPST2 and named them pst-1 and pst-2, respectively. We show that pst-1 is essential for viability in C. elegans, functions non-redundantly with pst-2, and can act non-autonomously to mediate essential functions. Additionally, pst-1 is required for specific aspects of nervous system development rather than for formation of the major neuronal ganglia or fascicles. Neuronal defects correlate with reduced complexity of HS modification patterns, as measured by direct biochemical analysis. Our results suggest that pst-1 functions in metazoans to establish the complex HS modification patterns that are required for the development of neuronal connectivity.

摘要

糖的硫酸化,如肝素硫酸酯 (HS) 或酪氨酸,需要将通用硫酸供体 3'-磷酸腺苷-5'-磷酸硫酸酯 (PAPS) 从细胞质转运到高尔基体。后生动物基因组编码两种假定的 PAPS 转运蛋白 (PAPST1 和 PAPST2),体外实验表明它们优先跨膜转运 PAPS。我们鉴定了秀丽隐杆线虫中 PAPST1 和 PAPST2 的直系同源物,并分别将它们命名为 pst-1 和 pst-2。我们表明,pst-1 在秀丽隐杆线虫中对生存至关重要,与 pst-2 非冗余,并且可以非自主发挥作用来介导必需的功能。此外,pst-1 对于神经系统发育的特定方面是必需的,而不是主要神经元神经节或束的形成。神经元缺陷与 HS 修饰模式的复杂性降低相关,这可以通过直接生化分析来衡量。我们的结果表明,pst-1 在后生动物中发挥作用,以建立复杂的 HS 修饰模式,这是神经元连接发育所必需的。

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本文引用的文献

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