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

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

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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.

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