Glycosyl Phosphatidylinositol Anchor Biosynthesis Is Essential for Maintaining Epithelial Integrity during Embryogenesis

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Cell surface proteins, such as receptors, either integrate into the plasma membrane through a transmembrane domain or are tethered to it by an accessory glycosylated phospholipid (GPI) anchor that is attached to them after they are made. The GPI-anchor biosynthesis pathway is highly conserved from yeast to humans and null mutations in any of the key enzymes are lethal at early developmental stages. Point mutations in several genes encoding for GPI-anchor biosynthesis enzymes have been linked to human disease. Specifically, mutations in PIGV are associated with multiple congenital malformations, including renal and anorectal malformation and mental retardation. It is currently not known how the mutations in PIGV lead to these diseases. Here we describe a point mutation in the PIGV ortholog of the nematode Caenorhabditis elegans, pigv-1, which is found to cause a high degree of embryonic lethality. We documented a substantial reduction in the level of GPI-anchors in the mutant. Importantly, following its development using 4D microscopy and employing tissue-specific rescue, we identified loss of epithelial integrity as the primary cause of developmental arrest. Our results highlight the importance of GPI-anchored proteins for epithelial integrity in vivo and suggest a possible etiology for human diseases associated with PIGV mutations.

Vyšlo v časopise: Glycosyl Phosphatidylinositol Anchor Biosynthesis Is Essential for Maintaining Epithelial Integrity during Embryogenesis. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005082
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005082

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