title: Drosophila GPI-mannosyltransferase 2 is required for GPI anchor attachment and surface expression of chaoptin.
abstract: 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.
authors.affiliation: Department of Ophthalmology & Visual Sciences, Department of Genetics, and The Eye Research Institute, University of Wisconsin, Madison, WI, USA.
authors.forename: Erica E
authors.initials: EE
authors.lastname: Rosenbaum
authors.forename: Kimberley S
authors.initials: KS
authors.lastname: Brehm
authors.forename: Eva
authors.initials: E
authors.lastname: Vasiljevic
authors.forename: Allen
authors.initials: A
authors.lastname: Gajeski
authors.forename: Nansi Jo
authors.initials: NJ
authors.lastname: Colley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D004247:DNA / Q000235:genetics; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008364:Mannosyltransferases / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008854:Microscopy, Electron; D008871:Microvilli / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D055355:Opsins / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D013045:Species Specificity
chemical_list: D029721:Drosophila Proteins; D017261:Glycosylphosphatidylinositols; D008562:Membrane Glycoproteins; D055355:Opsins; D011956:Receptors, Cell Surface; C055093:chp protein, Drosophila; D004247:DNA; D008364:Mannosyltransferases; C575675:veg protein, Drosophila