Drosophila GPI-mannosyltransferase 2 is required for GPI anchor attachment and surface expression of chaoptin.

Glycosylphosphatidylinositol (GPI) anchors are critical for the membrane attachment of a wide variety of essential signaling and cell adhesion proteins. The GPI anchor is a complex glycolipid structure that utilizes glycosylphosphatidylinositol-mannosyltransferases (GPI-MTs) for the addition of three core mannose residues during its biosynthesis. Here, we demonstrate that Drosophila GPI-MT2 is required for the GPI-mediated membrane attachment of several GPI-anchored proteins, including the photoreceptor-specific cell adhesion molecule, chaoptin. Mutations in gpi-mt2 lead to defects in chaoptin trafficking to the plasma membrane in Drosophila photoreceptor cells. In gpi-mt2 mutants, loss of sufficient chaoptin in the membrane leads to microvillar instability, photoreceptor cell pathology, and retinal degeneration. Finally, using site-directed mutagenesis, we have identified key amino acids that are essential for GPI-MT2 function and cell viability in Drosophila. Our findings on GPI-MT2 provide a mechanistic link between GPI anchor biosynthesis and protein trafficking in Drosophila and shed light on a novel mechanism for inherited retinal degeneration.

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