Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
PLoS Genet. 2023 Nov 6;19(11):e1011008. doi: 10.1371/journal.pgen.1011008. eCollection 2023 Nov.
The cuticles of ecdysozoan animals are barriers to material loss and xenobiotic insult. Key to this barrier is lipid content, the establishment of which is poorly understood. Here, we show that the p-glycoprotein PGP-14 functions coincidently with the sphingomyelin synthase SMS-5 to establish a polar lipid barrier within the pharyngeal cuticle of the nematode C. elegans. We show that PGP-14 and SMS-5 are coincidentally expressed in the epithelium that surrounds the anterior pharyngeal cuticle where PGP-14 localizes to the apical membrane. pgp-14 and sms-5 also peak in expression at the time of new cuticle synthesis. Loss of PGP-14 and SMS-5 dramatically reduces pharyngeal cuticle staining by Nile Red, a key marker of polar lipids, and coincidently alters the nematode's response to a wide-range of xenobiotics. We infer that PGP-14 exports polar lipids into the developing pharyngeal cuticle in an SMS-5-dependent manner to safeguard the nematode from environmental insult.
蜕皮动物的角质层是防止物质损失和外来物质侵害的屏障。这个屏障的关键是脂质含量,而脂质含量的建立还了解甚少。在这里,我们表明 P 糖蛋白 PGP-14 与神经鞘氨醇合酶 SMS-5 共同作用,在秀丽隐杆线虫的咽角质层内建立极性脂质屏障。我们表明,PGP-14 和 SMS-5 同时在前咽角质层周围的上皮细胞中表达,PGP-14 定位于顶膜。pgp-14 和 sms-5 的表达也在新角质层合成时达到峰值。PGP-14 和 SMS-5 的缺失显著降低了尼罗红对咽角质层的染色,尼罗红是极性脂质的关键标志物,同时也改变了线虫对多种外来物质的反应。我们推断 PGP-14 以 SMS-5 依赖的方式将极性脂质输出到发育中的咽角质层中,以保护线虫免受环境侵害。