Hostname: page-component-7c8c6479df-ws8qp Total loading time: 0 Render date: 2024-03-29T16:03:25.290Z Has data issue: false hasContentIssue false

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

Published online by Cambridge University Press:  10 May 2012

ERICA E. ROSENBAUM
Affiliation:
Department of Ophthalmology & Visual Sciences, Department of Genetics, and The Eye Research Institute, University of Wisconsin, Madison, Wisconsin Neuroscience Training Program, University of Wisconsin, Madison, Wisconsin
KIMBERLEY S. BREHM
Affiliation:
Department of Ophthalmology & Visual Sciences, Department of Genetics, and The Eye Research Institute, University of Wisconsin, Madison, Wisconsin
EVA VASILJEVIC
Affiliation:
Department of Ophthalmology & Visual Sciences, Department of Genetics, and The Eye Research Institute, University of Wisconsin, Madison, Wisconsin
ALLEN GAJESKI
Affiliation:
Department of Ophthalmology & Visual Sciences, Department of Genetics, and The Eye Research Institute, University of Wisconsin, Madison, Wisconsin
NANSI JO COLLEY*
Affiliation:
Department of Ophthalmology & Visual Sciences, Department of Genetics, and The Eye Research Institute, University of Wisconsin, Madison, Wisconsin
*
*Address correspondence and reprint requests to: Dr. Nansi Jo Colley, Department of Ophthalmology & Visual Sciences, K6/460, 600 Highland Avenue, Madison, WI, 53792. E-mail: njcolley@wisc.edu

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.

Type
Research Articles
Copyright
Copyright © Cambridge University Press 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Almeida, A.M., Murakami, Y., Layton, D.M., Hillmen, P., Sellick, G.S., Maeda, Y., Richards, S., Patterson, S., Kotsianidis, I., Mollica, L., Crawford, D.H., Baker, A., Ferguson, M., Roberts, I., Houlston, R., Kinoshita, T. & Karadimitris, A. (2006). Hypomorphic promoter mutation in PIGM causes inherited glycosylphosphatidylinositol deficiency. Nature Medicine 12, 846851.CrossRefGoogle ScholarPubMed
Arrighi, R.B. & Faye, I. (2010). Plasmodium falciparum GPI toxin: A common foe for man and mosquito. Acta Tropica 114, 162165.Google Scholar
Bech-Hansen, N.T., Naylor, M.J., Maybaum, T.A., Sparkes, R.L., Koop, B., Birch, D.G., Bergen, A.A., Prinsen, C.F., Polomeno, R.C., Gal, A., Drack, A.V., Musarella, M.A., Jacobson, S.G., Young, R.S. & Weleber, R.G. (2000). Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness. Nature Genetics 26, 319323.Google Scholar
Bessler, M., Mason, P.J., Hillmen, P., Miyata, T., Yamada, N., Takeda, J., Luzzatto, L. & Kinoshita, T. (1994). Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene. The EMBO Journal 13, 110117.CrossRefGoogle ScholarPubMed
Chen, K.F., Peschel, N., Zavodska, R., Sehadova, H. & Stanewsky, R. (2011). QUASIMODO, a Novel GPI-anchored zona pellucida protein involved in light input to the Drosophila circadian clock. Current Biology 21, 719729.Google Scholar
Colley, N.J. (2010). Retinal degeneration through the eye of the fly. Encyclopedia of the Eye 4, 5461.CrossRefGoogle Scholar
Colley, N.J., Baker, E.K., Stamnes, M.A. & Zuker, C.S. (1991). The cyclophilin homolog ninaA is required in the secretory pathway. Cell 67, 255263.CrossRefGoogle ScholarPubMed
Colley, N.J., Cassill, J.A., Baker, E.K. & Zuker, C.S. (1995). Defective intracellular transport is the molecular basis of rhodopsin-dependent dominant retinal degeneration. Proceedings of the National Academy of Sciences of the United States of America 92, 30703074.CrossRefGoogle ScholarPubMed
Cordy, J.M., Hussain, I., Dingwall, C., Hooper, N.M. & Turner, A.J. (2003). Exclusively targeting beta-secretase to lipid rafts by GPI-anchor addition up-regulates beta-site processing of the amyloid precursor protein. Proceedings of the National Academy of Sciences of the United States of America 100, 1173511740.Google Scholar
David, S., Fry, E.J. & Lopez-Vales, R. (2008). Novel roles for Nogo receptor in inflammation and disease. Trends in Neurosciences 31, 221226.CrossRefGoogle Scholar
Fabre, A.L., Orlean, P. & Taron, C.H. (2005). Saccharomyces cerevisiae Ybr004c and its human homologue are required for addition of the second mannose during glycosylphosphatidylinositol precursor assembly. The FEBS Journal 272, 11601168.CrossRefGoogle ScholarPubMed
Fain, G.L., Hardie, R. & Laughlin, S.B. (2010). Phototransduction and the evolution of photoreceptors. Current Biology 20, R114R124.CrossRefGoogle ScholarPubMed
Faivre-Sarrailh, C., Banerjee, S., Li, J., Hortsch, M., Laval, M. & Bhat, M.A. (2004). Drosophila contactin, a homolog of vertebrate contactin, is required for septate junction organization and paracellular barrier function. Development 131, 49314942.CrossRefGoogle ScholarPubMed
Franceschini, N. (1972). Pupil and pseudopupil in the compound eye of Drosophila. In Information Processing in the Visual Systems of Arthropods, ed. Wehner, R., pp. 7582. Berlin, Germany: Springer-Verlag.Google Scholar
Franceschini, N. & Kirschfeld, K. (1971). Pseudopupil phenomena in the Drosophila compound eye. Kybernetik 9, 159182.CrossRefGoogle Scholar
Fujita, M. & Jigami, Y. (2008). Lipid remodeling of GPI-anchored proteins and its function. Biochimica et Biophysica Acta 1780, 410420.CrossRefGoogle ScholarPubMed
Grimme, S.J., Westfall, B.A., Wiedman, J.M., Taron, C.H. & Orlean, P. (2001). The essential Smp3 protein is required for addition of the side-branching fourth mannose during assembly of yeast glycosylphosphatidylinositols. The Journal of Biological Chemistry 276, 2773127739.CrossRefGoogle ScholarPubMed
Hardie, R.C. & Postma, M. (2008). Phototransduction in Microvillar Photoreceptors of Drosophila and Other Invertebrates, Vol. 1. San Diego, CA: Academic Press.Google Scholar
Hardie, R.C. & Raghu, P. (2001). Visual transduction in Drosophila. Nature 413, 186193.CrossRefGoogle ScholarPubMed
Hicks, D., John, D., Makova, N.Z., Henderson, Z., Nalivaeva, N.N. & Turner, A.J. (2011). Membrane targeting, shedding and protein interactions of brain acetylcholinesterase. Journal of Neurochemistry 116, 742746.CrossRefGoogle ScholarPubMed
Hirai-Fujita, Y., Yamamoto-Hino, M., Kanie, O. & Goto, S. (2008). N-Glycosylation of the Drosophila neural protein Chaoptin is essential for its stability, cell surface transport and adhesive activity. FEBS Letters 582, 25722576.Google Scholar
Kang, J.Y., Hong, Y., Ashida, H., Shishioh, N., Murakami, Y., Morita, Y.S., Maeda, Y. & Kinoshita, T. (2005). PIG-V involved in transferring the second mannose in glycosylphosphatidylinositol. The Journal of Biological Chemistry 280, 94899497.CrossRefGoogle ScholarPubMed
Kania, A., Salzberg, A., Bhat, M., D’Evelyn, D., He, Y., Kiss, I. & Bellen, H.J. (1995). P-element mutations affecting embryonic peripheral nervous system development in Drosophila melanogaster. Genetics 139, 16631678.CrossRefGoogle ScholarPubMed
Kanie, Y., Yamamoto-Hino, M., Karino, Y., Yokozawa, H., Nishihara, S., Ueda, R., Goto, S. & Kanie, O. (2009). Insight into the regulation of glycan synthesis in Drosophila chaoptin based on mass spectrometry. PLoS One 4, e5434.CrossRefGoogle ScholarPubMed
Karagogeos, D. (2003). Neural GPI-anchored cell adhesion molecules. Frontiers in Bioscience 8, s1304s1320.Google Scholar
Katz, B. & Minke, B. (2009). Drosophila photoreceptors and signaling mechanisms. Frontiers in Cellular Neuroscience 3, 2.Google Scholar
Kawagoe, K., Kitamura, D., Okabe, M., Taniuchi, I., Ikawa, M., Watanabe, T., Kinoshita, T. & Takeda, J. (1996). Glycosylphosphatidylinositol-anchor-deficient mice: Implications for clonal dominance of mutant cells in paroxysmal nocturnal hemoglobinuria. Blood 87, 36003606.CrossRefGoogle ScholarPubMed
Khandhadia, S., Cipriani, V., Yates, J.R. & Lotery, A.J. (2011). Age-related macular degeneration and the complement system. Immunobiology 217, 127146.CrossRefGoogle ScholarPubMed
Kinoshita, T., Fujita, M. & Maeda, Y. (2008). Biosynthesis, remodelling and functions of mammalian GPI-anchored proteins: Recent progress. Journal of Biochemistry 144, 287294.Google Scholar
Koundakjian, E.J., Cowan, D.M., Hardy, R.W. & Becker, A.H. (2004). The Zuker collection: A resource for the analysis of autosomal gene function in Drosophila melanogaster. Genetics 167, 203206.Google Scholar
Krantz, D.E. & Zipursky, S.L. (1990). Drosophila chaoptin, a member of the leucine-rich repeat family, is a photoreceptor cell-specific adhesion molecule. The EMBO Journal 6, 19691977.Google Scholar
Laemmli, U.K. (1970). Cleavage of structural proteins during assembly of the head of bacteriophage T4. Nature 227, 680685.Google Scholar
Leidich, S.D., Drapp, D.A. & Orlean, P. (1994). A conditionally lethal yeast mutant blocked at the first step in glycosyl phosphatidylinositol anchor synthesis. The Journal of Biological Chemistry 269, 1019310196.Google Scholar
Levental, I., Grzybek, M. & Simons, K. (2010). Greasing their way: Lipid modifications determine protein association with membrane rafts. Biochemistry 49, 63056316.CrossRefGoogle ScholarPubMed
Lopez-Pedrera, C., Aguirre, M.A., Barbarroja, N. & Cuadrado, M.J. (2010). Accelerated atherosclerosis in systemic lupus erythematosus: Role of proinflammatory cytokines and therapeutic approaches. Journal of Biomedicine & Biotechnology, pii: 607084, Epub 2010 Sep 26.CrossRefGoogle ScholarPubMed
Ma, K.N., Cashman, S.M., Sweigard, J.H. & Kumar-Singh, R. (2010). Decay accelerating factor (CD55)-mediated attenuation of complement: Therapeutic implications for age-related macular degeneration. Investigative Ophthalmology & Visual Science 51, 67766783.Google Scholar
Maeda, Y. & Kinoshita, T. (2011). Structural remodeling, trafficking and functions of glycosylphosphatidylinositol-anchored proteins. Progress in Lipid Research 50, 411424.Google Scholar
Maxwell, S.E., Ramalingam, S., Gerber, L.D., Brink, L. & Udenfriend, S. (1995 a). An active carbonyl formed during glycosylphosphatidylinositol addition to a protein is evidence of catalysis by a transamidase. The Journal of Biological Chemistry 270, 1957619582.CrossRefGoogle ScholarPubMed
Maxwell, S.E., Ramalingam, S., Gerber, L.D. & Udenfriend, S. (1995 b). Cleavage without anchor addition accompanies the processing of a nascent protein to its glycosylphosphatidylinositol-anchored form. Proceedings of the National Academy of Sciences of the United States of America 92, 15501554.CrossRefGoogle ScholarPubMed
Maydan, G., Noyman, I., Har-Zahav, A., Neriah, Z.B., Pasmanik-Chor, M., Yeheskel, A., Albin-Kaplanski, A., Maya, I., Magal, N., Birk, E., Simon, A.J., Halevy, A., Rechavi, G., Shohat, M., Straussberg, R. & Basel-Vanagaite, L. (2011). Multiple congenital anomalies-hypotonia-seizures syndrome is caused by a mutation in PIGN. Journal of Medical Genetics 48, 383389.CrossRefGoogle ScholarPubMed
Nagamune, K., Ohishi, K., Ashida, H., Hong, Y., Hino, J., Kangawa, K., Inoue, N., Maeda, Y. & Kinoshita, T. (2003). GPI transamidase of Trypanosoma brucei has two previously uncharacterized (trypanosomatid transamidase 1 and 2) and three common subunits. Proceedings of the National Academy of Sciences of the United States of America 100, 1068210687.Google Scholar
Nozaki, M., Ohishi, K., Yamada, N., Kinoshita, T., Nagy, A. & Takeda, J. (1999). Developmental abnormalities of glycosylphosphatidylinositol-anchor-deficient embryos revealed by Cre/loxP system. Laboratory Investigation 79, 293299.Google ScholarPubMed
O’Connor, E., Eisenhaber, B., Dalley, J., Wang, T., Missen, C., Bulleid, N., Bishop, P.N. & Trump, D. (2005). Species specific membrane anchoring of nyctalopin, a small leucine-rich repeat protein. Human Molecular Genetics 14, 18771887.CrossRefGoogle ScholarPubMed
Oriol, R., Martinez-Duncker, I., Chantret, I., Mollicone, R. & Codogno, P. (2002). Common origin and evolution of glycosyltransferases using Dol-P-monosaccharides as donor substrate. Molecular Biology and Evolution 19, 14511463.CrossRefGoogle ScholarPubMed
Orlean, P., Leidich, S.D., Drapp, D.A. & Colussi, P. (1994). Isolation of temperature-sensitive yeast GPI-anchoring mutants. Brazilian Journal of Medical and Biological Research 27, 145150.Google Scholar
Orlean, P. & Menon, A.K. (2007). GPI anchoring of protein in yeast and mammalian cells, or: How we learned to stop worrying and love glycophospholipids. Journal of Lipid Research 48, 9931011.Google ScholarPubMed
Ortonne, N., Ram-Wolff, C., Giustiniani, J., Marie-Cardine, A., Bagot, M., Mecheri, S. & Bensussan, A. (2011). Human and mouse mast cells express and secrete the GPI-anchored isoform of CD160. The Journal of Investigative Dermatology 131, 916924.CrossRefGoogle ScholarPubMed
Pang, S., Urquhart, P. & Hooper, N.M. (2004). N-glycans, not the GPI anchor, mediate the apical targeting of a naturally glycosylated, GPI-anchored protein in polarised epithelial cells. Journal of Cell Science 117, 50795086.CrossRefGoogle Scholar
Paulick, M.G. & Bertozzi, C.R. (2008). The glycosylphosphatidylinositol anchor: A complex membrane-anchoring structure for proteins. Biochemistry 47, 69917000.CrossRefGoogle ScholarPubMed
Prokopenko, S.N., He, Y., Lu, Y. & Bellen, H.J. (2000). Mutations affecting the development of the peripheral nervous system in Drosophila: A molecular screen for novel proteins. Genetics 156, 16911715.CrossRefGoogle ScholarPubMed
Pusch, C.M., Zeitz, C., Brandau, O., Pesch, K., Achatz, H., Feil, S., Scharfe, C., Maurer, J., Jacobi, F.K., Pinckers, A., Andreasson, S., Hardcastle, A., Wissinger, B., Berger, W. & Meindl, A. (2000). The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein. Nature Genetics 26, 324327.Google Scholar
Radford, H.E. & Mallucci, G.R. (2010). The role of GPI-anchored PrP C in mediating the neurotoxic effect of scrapie prions in neurons. Current Issues in Molecular Biology 12, 119127.Google Scholar
Ramo, K., Cashman, S.M. & Kumar-Singh, R. (2008). Evaluation of adenovirus-delivered human CD59 as a potential therapy for AMD in a model of human membrane attack complex formation on murine RPE. Investigative Ophthalmology & Visual Science 49, 41264136.CrossRefGoogle Scholar
Rosenbaum, E.E., Hardie, R.C. & Colley, N.J. (2006). Calnexin is essential for rhodopsin maturation, Ca2+ regulation, and photoreceptor cell survival. Neuron 49, 229241.Google Scholar
Ruiz, P., Weppler, D., Tryphonopoulos, P., Nishida, S., Moon, J., Kato, T., Selvaggi, G., Levi, D., Madariaga, J., DelaGarza, J., Tuteja, S., Garcia, M. & Tzakis, A. (2006). CD55 and CD59 deficiency in transplant patient populations: Possible association with paroxysmal nocturnal hemoglobinuria-like symptoms in Campath-treated patients. Transplantation Proceedings 38, 17501752.Google Scholar
Sharom, F.J. & Lehto, M.T. (2002). Glycosylphosphatidylinositol-anchored proteins: Structure, function, and cleavage by phosphatidylinositol-specific phospholipase C. Biochemistry and Cell Biology 80, 535549.CrossRefGoogle ScholarPubMed
Sheffield, V.C. & Stone, E.M. (2011). Genomics and the eye. The New England Journal of Medicine 364, 19321942.Google Scholar
Spurway, T.D., Dalley, J.A., High, S. & Bulleid, N.J. (2001). Early events in glycosylphosphatidylinositol anchor addition. substrate proteins associate with the transamidase subunit gpi8p. The Journal of Biological Chemistry 276, 1597515982.CrossRefGoogle ScholarPubMed
Tiede, A., Bastisch, I., Schubert, J., Orlean, P. & Schmidt, R.E. (1999). Biosynthesis of glycosylphosphatidylinositols in mammals and unicellular microbes. Biological Chemistry 380, 503523.CrossRefGoogle ScholarPubMed
Tremml, G., Dominguez, C., Rosti, V., Zhang, Z., Pandolfi, P.P., Keller, P. & Bessler, M. (1999). Increased sensitivity to complement and a decreased red blood cell life span in mice mosaic for a nonfunctional Piga gene. Blood 94, 29452954.CrossRefGoogle Scholar
Vagin, O., Kraut, J.A. & Sachs, G. (2009). Role of N-glycosylation in trafficking of apical membrane proteins in epithelia. American Journal of Physiology. Renal Physiology 296, F459F469.Google Scholar
Van Vactor, D. Jr, Krantz, D.E., Reinke, R. & Zipursky, S.L. (1988). Analysis of mutants in Chaoptin, a photoreceptor cell-specific glycoprotein in Drosophila, reveals its role in cellular morphogenesis. Cell 52, 281290.CrossRefGoogle ScholarPubMed
Varma, Y. & Hendrickson, T. (2010). Methods to study GPI anchoring of proteins. Chembiochem 11, 623636.CrossRefGoogle ScholarPubMed
Veerhuis, R. (2011). Histological and direct evidence for the role of complement in the neuroinflammation of AD. Current Alzheimer Research 8, 3458.CrossRefGoogle ScholarPubMed
Veerhuis, R., Nielsen, H.M. & Tenner, A.J. (2011). Complement in the brain. Molecular Immunology 48, 15921603.CrossRefGoogle ScholarPubMed
Vetrivel, K.S., Barman, A., Chen, Y., Nguyen, P.D., Wagner, S.L., Prabhakar, R. & Thinakaran, G. (2011). Loss of cleavage at beta’-site contributes to apparent increase in beta-amyloid peptide (Abeta) secretion by beta-secretase (BACE1)-glycosylphosphatidylinositol (GPI) processing of amyloid precursor protein. The Journal of Biological Chemistry 286, 2616626177.Google Scholar
Wang, T. & Montell, C. (2007). Phototransduction and retinal degeneration in Drosophila. Pflügers Archiv 454, 821847.Google Scholar
Yau, K.W. & Hardie, R.C. (2009). Phototransduction motifs and variations. Cell 139, 246264.Google Scholar
Zeitz, C., Scherthan, H., Freier, S., Feil, S., Suckow, V., Schweiger, S. & Berger, W. (2003). NYX (nyctalopin on chromosome X), the gene mutated in congenital stationary night blindness, encodes a cell surface protein. Investigative Ophthalmology & Visual Science 44, 41844191.Google Scholar
Zhang, J., Gerhardinger, C. & Lorenzi, M. (2002). Early complement activation and decreased levels of glycosylphosphatidylinositol-anchored complement inhibitors in human and experimental diabetic retinopathy. Diabetes 51, 34993504.Google Scholar