Berardinelli, Steven - The University of Georgia - Department of Biochemistry & Molecular Biology

研究领域

Glycobiology is a relatively young field that focuses on examining the biological effects of modifying proteins and lipids with carbohydrates. Glycans provide incredible structural diversity to biological systems, offering the potential to alter function in a wide variety of ways, but also bringing significant technical challenges for structural analysis. Advances in methodologies to examine these structures has brought significant insight into functions for glycans in a wide variety of biological contexts over the past decade, causing rapid growth and interest in the field. My laboratory focuses on the role of carbohydrate modifications on proteins, especially as they affect cellular communication events. Protein glycosylation exists in two major forms: N-linked, referring to glycans linked to protein through the amide nitrogen of asparagine residues, and O-linked, where the glycans are linked through the hydroxyl groups of serine or threonine. O-Glycans are divided into subclasses based on the carbohydrate linked directly to the serine or threonine. The subclasses that we focus on are called O-fucose and O-glucose. All of the projects in the laboratory deal with learning more about these forms of glycosylation. Several are discussed in more detail below.

近期论文

查看导师新发文章（温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

S.M. Thakurdas, M.F. Lopez, S. Kakuda, R. Fernandez-Valdivia, N. Zarrin-Khameh, R.S. Haltiwanger, H. Jafar-Nejad. 2016. Jagged1 heterozygosity in mice results in a congenital cholangiopathy which is reversed by concomitant deletion of one copy of Poglut1 (Rumi). Hepatology 63: 550-565. E Servian-Morilla, H Takeuchi, TV Lee, J Clarimon, F Mavillard, E Area-Gomez, E Rivas, JL Nieto-Gonzalez, MC Rivero, M Cabrera-Serrano, L Gomez-Sanchez, JA Martinez-Lopez, B Estrada, C Marquez, Y Morgado, X Suarez-Calvet, G JPita, A Bigot, E Gallardo, R Fernandez-Chachon, M Hirano, RS Haltiwanger, H Jara-Nejad, C Parada. 2016. A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss. EMBO Mol Med 8: 1289-1309 J Dubail, D Vasudevan, SE Earp, MW Jenkins, RS Haltiwanger, SS Apte. 2016. Impaired ADAMTS9 secretion: A potential mechanism for eye defects in Peters Plus Syndrome. Sci Rep 6: 33974-. H Yu, H Takeuchi, M Takeuchi, Q Liu, J Kantharia, RS Haltiwanger, H Liu. 2016. Structural analysis of Notch-regulating Rumi reveals basis for pathogenic mutations. Nat Chem Biol 12: 735-740 B Benz, S Nandadasa, M Takeuchi, RC Grady, H Takeuchi, RK LoPilato, S Kakuda, RPT Somerville, SS Apte, RS Haltiwanger, BC Holdener. 2016. Genetic and biochemical evidence that gastrulation defects in Pofut2 mutants result from defects in ADAMTS9 secretion. Dev Biol 416: 111-122 BM Harvey, NA Rana, H Moss, J Leonardi, H Jafar-Nejad, RS Haltiwanger. 2016. Mapping Sites of O-Glycosylation and Fringe Elongation on Drosophila Notch. J Biol Chem 291: 16348-16360 J Valero-Gonzalez, C Leohhard-Melief, E Lira-Naverrete, G Jimenz-Oses, C Hernandez-Ruiz, MC Pallares, I Yruela, D Vasudevan, A Lostao, F Corzana, H Takeuchi, RS Haltiwanger, R Hurtado-Guerrero. 2016. A proactive role of water molecules in acceptor recognition by protein O-fucosyltransferase 2. Nat Chem Biol 12: 240-246. PMID:26854667 D. Vasudevan, H. Takeuchi, S.S. Johar, E. Majerus, R.S. Haltiwanger. 2015. Peters plus syndrome mutations disrupt a noncanonical ER quality-control mechanism. Curr. Biol. 25: 286-295. PMID:25544610 H Yu, M Takeuchi, J LeBarron, J. Kantharia, E London, H. Bakker, RS Haltiwanger, H. Li, H. Takeuchi. 2015. Notch-modifying xylosyltransferase structures support an SNi-like retaining mechanism. Nat Chem Biol 11: 847-854. PMID:26414444 N Ramkumar, BM Harvey, JD Lee, HL Alcorn, NF Silva-Gagliardi, CJ McGlade, TH Bestor, J Wijnholds, RS Haltiwanger, KV Anderson. 2015. Proten O-Glucosyltransferase 1 (POGLUT1) Promotes Mouse Gastrulation through Modification of the Apical Polarity Protein CRUMBS2. PLoS Genetics 11(10): e1005551-. PMID:26496195 J. Muller, N.A. Rana, K. Serth, S. Kakuda, R.S. Haltiwanger, A. Gossler. 2014. O-Fucosylation of the Notch ligand mDLL1 by POFUT1 is dispensible for ligand function. PLoS One 9: e88571-. PMID:24533113 P. Taylor, H. Takeuchi, D. Sheppard, C. Chillakuri, SM Lea, R.S. Haltiwanger, P.A. Handford. 2014. Fringe-mediated extension of O-linkedfucose in the ligand-binding region of Notch1 increases binding to mammalian Notch ligands. Proc. Natl. Acad. Sci. USA 111: 7290-7295. PMID:24803430 A.R. Haltom, T.V. Lee, B.M. Harvey, J. Leonardi, Y.J. Chen, Y. Hong, R.S. Haltiwanger, H. Jafar-Nejad. 2014. The protein O-glycosyltransferase Rumi modifies eyes shut to promote rhabdomere separation in Drosophila. PLoS Genet. 10: e1004795-. PMID:25412384 E. Al-Shareffi, J.-L. Chaubard, C. Leonhard-Melief, S.-K. Wang, C.-H. Wong, R.S. Haltiwanger. 2013. 6-Alkynyl fucose is a bioorthogonal analogue for O-fucosylation of epidermal growth factor-like repeats and thrombospondin type-1 repeats by protein O-fucosyltransferases 1 and 2. Glycobiology 23: 188-198. PMID:23045360 T.V. Lee, M.K. Sethi, J. Leonardi, N.A. Rana, F.F.R. Buettner, R.S. Haltiwanger, H. Bakker, H. Jafar-Nejad. 2013. Negative regulation of Notch signaling by xylose. PLoS Genet. 9: e1003547-. PMID:23754965 M.K. Sethi, F.F>R. Buettner, A. Ashikov, V.B. Krylov, H. Takeuchi, N.E. Nifantiev, R.S. Haltiwanger, R. Gerardy-Schahn, H. Bakker. 2012. Molecular cloning of a xylosyltransferase that transfer the second xylose to O-glucosylated epidermal growth factor repeats of Notch. J. Biol. Chem. 287: 2739-2748. PMID:22117070 H. Takeuchi, J. Kantharia, M.K. Sethi, H. Bakker, R.S. Haltiwanger. 2012. Site-specific O-glucosylation of the epidermal growth factor-like (EGF) repeats of Notch: Efficiency of glycosylation is affected by proper folding and amino acid sequence of individual EGF repeats. J. Biol. Chem. 287: 33934-33944. PMID:22872643 S. Yamamoto, W.-L. Charng, N.A. Rana, S. Kakuda, M. Jaiswal, V. Bayat, B. Xiong, K. Zhang, H. Sandoval, G. David, H. Wang, R.S. Haltiwanger, H.J. Bellen. 2012. A mutation in EGF repeat-8 of Notch discriminates between Serrate/Jagged and Delta family ligands. Science 338: 1229-1232. PMID:23197537 R. Fernandez-Valdivia, H. Takeuchi, A. Samarghandi, M. Lopez, J. Leonardi, R.S. Haltiwanger, H. Jafar-Nejad. 2011. Regulation of the mammalian Notch signaling and embryonic development by the protein O-glucosyltransferase Rumi. Development 138: 1925-1934. PMID:21490058 N.A. Rana, A. Nita-Lazar, H. Takeuchi, S. Kakuda, K.B. Luther, R.S. Haltiwanger. 2011. O-Glucose trisaccharide is present at high but variable stoichiometry at multiple sites on mouse Notch1. J. Biol. Chem. 286: 31623-31637. PMID:21757702 H. Takeuchi, R.C. Fernandez-Valdivia, D.S. Caswell, A. Nita-Lazar, N.A. Rana, T. Garner, T. Weldegheorghis, M.A. Macnaughtan, H. Jafar-Nejad, R.S. Haltiwanger. 2011. Rumi functions as both a protein O-glucosyltransferase and a protein O-xylosyltransferase. Proc. Natl. Acad. Sci. USA 108: 16600-16605. PMID:21949356 M.K. Sethi, F.F.R. Buettner, V.B. Krylov, H. Takeuchi, N.E. Nifantiev, R.S. Haltiwanger, R. Gerardy-Schahn, H. Bakker. 2010. Identification of glycosyltransferase 8 family members as xylosyltransferases actin on O-glucosylated Notch EGF repeats. J. Biol. Chem. 285: 1582-1585. PMID:19940119 J. Du, H. Takeuchi, C. Leonhard-Melief, K.R. Shroyer, M. Dlugosz, R.S. Haltiwanger, B.C. Holdener. 2010. O-Fucosylation of thrombospondin type 1 repeats restricts epithelial to mesenchymal transition (EMT) and maintains epiblast pluripotency during mouse gastrulation. Dev. Biol. 346: 25-38. PMID:20637190 K.B. Luther, H. Schindelin, R.S. Haltiwanger. 2009. Structural and mechanistic insights into Lunatic Fringe from a kinetic analysis of enzyme mutants. J. Biol. Chem. 284: 3294-3305. PMID:19028689