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Title: A molecular switch orchestrates enzyme specificity and secretory granule morphology

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Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
Resource Type:
Journal Article
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2041-1723
Nature Publishing Group
Country of Publication:
United States

Citation Formats

Ji, Suena, Samara, Nadine L., Revoredo, Leslie, Zhang, Liping, Tran, Duy T., Muirhead, Kayla, Tabak, Lawrence A., and Ten Hagen, Kelly G. A molecular switch orchestrates enzyme specificity and secretory granule morphology. United States: N. p., 2018. Web. doi:10.1038/s41467-018-05978-9.
Ji, Suena, Samara, Nadine L., Revoredo, Leslie, Zhang, Liping, Tran, Duy T., Muirhead, Kayla, Tabak, Lawrence A., & Ten Hagen, Kelly G. A molecular switch orchestrates enzyme specificity and secretory granule morphology. United States. doi:10.1038/s41467-018-05978-9.
Ji, Suena, Samara, Nadine L., Revoredo, Leslie, Zhang, Liping, Tran, Duy T., Muirhead, Kayla, Tabak, Lawrence A., and Ten Hagen, Kelly G. Wed . "A molecular switch orchestrates enzyme specificity and secretory granule morphology". United States. doi:10.1038/s41467-018-05978-9.
title = {A molecular switch orchestrates enzyme specificity and secretory granule morphology},
author = {Ji, Suena and Samara, Nadine L. and Revoredo, Leslie and Zhang, Liping and Tran, Duy T. and Muirhead, Kayla and Tabak, Lawrence A. and Ten Hagen, Kelly G.},
abstractNote = {},
doi = {10.1038/s41467-018-05978-9},
journal = {Nature Communications},
issn = {2041-1723},
number = 1,
volume = 9,
place = {United States},
year = {2018},
month = {8}

Works referenced in this record:

Colorectal Cancer in Mice Genetically Deficient in the Mucin Muc2
journal, March 2002

Loss of the mucosal barrier alters the progenitor cell niche via Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling
journal, November 2017

  • Zhang, Liping; Turner, Bradley; Ribbeck, Katharina
  • Journal of Biological Chemistry, Vol. 292, Issue 52
  • DOI: 10.1074/jbc.M117.809848

Defective Intestinal Mucin-Type O-Glycosylation Causes Spontaneous Colitis-Associated Cancer in Mice
journal, July 2016

Overview of the CCP 4 suite and current developments
journal, March 2011

  • Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
  • DOI: 10.1107/S0907444910045749

Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis
journal, February 2013

Type II phosphatidylinositol 4-kinase regulates trafficking of secretory granule proteins in Drosophila
journal, July 2012

  • Burgess, J.; Del Bel, L. M.; Ma, C. -I. J.
  • Development, Vol. 139, Issue 16
  • DOI: 10.1242/dev.077644

Structural Basis of Carbohydrate Transfer Activity by Human UDP-GalNAc: Polypeptide α-N-Acetylgalactosaminyltransferase (pp-GalNAc-T10)
journal, June 2006

  • Kubota, Tomomi; Shiba, Tomoo; Sugioka, Shigemi
  • Journal of Molecular Biology, Vol. 359, Issue 3
  • DOI: 10.1016/j.jmb.2006.03.061

New Helical Binding Domain Mediates a Glycosyltransferase Activity of a Bifunctional Protein
journal, August 2016

  • Zhang, Hua; Zhou, Meixian; Yang, Tiandi
  • Journal of Biological Chemistry, Vol. 291, Issue 42
  • DOI: 10.1074/jbc.M116.731695

The beginnings of mucin biosynthesis: The crystal structure of UDP-GalNAc:polypeptide  -N-acetylgalactosaminyltransferase-T1
journal, October 2004

  • Fritz, T. A.; Hurley, J. H.; Trinh, L. -B.
  • Proceedings of the National Academy of Sciences, Vol. 101, Issue 43
  • DOI: 10.1073/pnas.0405657101

The Catalytic and Lectin Domains of UDP-GalNAc:Polypeptide α- N -Acetylgalactosaminyltransferase Function in Concert to Direct Glycosylation Site Selection
journal, June 2008

  • Raman, Jayalakshmi; Fritz, Timothy A.; Gerken, Thomas A.
  • Journal of Biological Chemistry, Vol. 283, Issue 34
  • DOI: 10.1074/jbc.M803387200

Immunological aspects of intestinal mucus and mucins
journal, August 2016

  • Johansson, Malin E. V.; Hansson, Gunnar C.
  • Nature Reviews Immunology, Vol. 16, Issue 10
  • DOI: 10.1038/nri.2016.88

Muc2-Deficient Mice Spontaneously Develop Colitis, Indicating That MUC2 Is Critical for Colonic Protection
journal, July 2006

  • Van der Sluis, Maria; De Koning, Barbara A. E.; De Bruijn, Adrianus C. J. M.
  • Gastroenterology, Vol. 131, Issue 1
  • DOI: 10.1053/j.gastro.2006.04.020

Principles of Mucin Architecture:  Structural Studies on Synthetic Glycopeptides Bearing Clustered Mono-, Di-, Tri-, and Hexasaccharide Glycodomains
journal, August 2002

  • Coltart, Don M.; Royyuru, Ajay K.; Williams, Lawrence J.
  • Journal of the American Chemical Society, Vol. 124, Issue 33
  • DOI: 10.1021/ja020208f

The recombinant C-terminus of the human MUC2 mucin forms dimers in Chinese-hamster ovary cells and heterodimers with full-length MUC2 in LS 174T cells
journal, June 2003

  • Lidell, Martin E.; Johansson, Malin E. V.; MÖRgelin, Matthias
  • Biochemical Journal, Vol. 372, Issue 2
  • DOI: 10.1042/bj20030003

GLUT4 exocytosis
journal, December 2011

  • Stöckli, Jacqueline; Fazakerley, Daniel J.; James, David E.
  • Journal of Cell Science, Vol. 124, Issue 24
  • DOI: 10.1242/jcs.097063

Defective goblet cell exocytosis contributes to murine cystic fibrosis–associated intestinal disease
journal, February 2015

  • Liu, Jinghua; Walker, Nancy M.; Ootani, Akifumi
  • Journal of Clinical Investigation, Vol. 125, Issue 3
  • DOI: 10.1172/JCI73193

pH-dependent processing of secretogranin II by the endopeptidase PC2 in isolated immature secretory granules
journal, January 1997

  • UrbÉ, Sylvie; DittiÉ, Andrea S.; Tooze, Sharon A.
  • Biochemical Journal, Vol. 321, Issue 1
  • DOI: 10.1042/bj3210065

Glycobiology on the fly: Developmental and mechanistic insights from Drosophila
journal, October 2008

Secretory Protein Biogenesis and Traffic in the Early Secretory Pathway
journal, February 2013

Homotypic Fusion of Immature Secretory Granules During Maturation Requires Syntaxin 6
journal, June 2001

  • Wendler, Franz; Page, Lesley; Urbé, Sylvie
  • Molecular Biology of the Cell, Vol. 12, Issue 6
  • DOI: 10.1091/mbc.12.6.1699

Mucin-type O -Glycosylation during Development
journal, January 2013

  • Tran, Duy T.; Ten Hagen, Kelly G.
  • Journal of Biological Chemistry, Vol. 288, Issue 10
  • DOI: 10.1074/jbc.R112.418558

journal, January 1999

  • Osborne, Shona L.; Herreros, Judit; Bastiaens, Philippe I. H.
  • Journal of Biological Chemistry, Vol. 274, Issue 1
  • DOI: 10.1074/jbc.274.1.59

Loss of intestinal O -glycans promotes spontaneous duodenal tumors
journal, July 2016

  • Gao, Nan; Bergstrom, Kirk; Fu, Jianxin
  • American Journal of Physiology-Gastrointestinal and Liver Physiology, Vol. 311, Issue 1
  • DOI: 10.1152/ajpgi.00060.2016

Substrate-Guided Front-Face Reaction Revealed by Combined Structural Snapshots and Metadynamics for the Polypeptide N -Acetylgalactosaminyltransferase 2
journal, June 2014

  • Lira-Navarrete, Erandi; Iglesias-Fernández, Javier; Zandberg, Wesley F.
  • Angewandte Chemie International Edition, Vol. 53, Issue 31
  • DOI: 10.1002/anie.201402781

Glue Secretion in the Drosophila Salivary Gland: A Model for Steroid-Regulated Exocytosis
journal, March 2001

Role of glycosylation on the conformation and chain dimensions of O-linked glycoproteins: light-scattering studies of ovine submaxillary mucin
journal, June 1989

  • Shogren, Randal; Gerken, Thomas A.; Jentoft, Neil
  • Biochemistry, Vol. 28, Issue 13
  • DOI: 10.1021/bi00439a029

A Drosophila salivary gland mucin is also expressed in immune tissues: evidence for a function in coagulation and the entrapment of bacteria
journal, December 2004

  • Korayem, Ahmed M.; Fabbri, Marco; Takahashi, Kuniaki
  • Insect Biochemistry and Molecular Biology, Vol. 34, Issue 12
  • DOI: 10.1016/j.ibmb.2004.09.001

Recent structural and mechanistic insights into post-translational enzymatic glycosylation
journal, December 2012

  • Hurtado-Guerrero, Ramon; Davies, Gideon J.
  • Current Opinion in Chemical Biology, Vol. 16, Issue 5-6
  • DOI: 10.1016/j.cbpa.2012.10.013

UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyltransferases: Completion of the family tree
journal, December 2011

  • Raman, Jayalakshmi; Guan, Yu; Perrine, Cynthia L.
  • Glycobiology, Vol. 22, Issue 6
  • DOI: 10.1093/glycob/cwr183

Control of mucin-type O-glycosylation: A classification of the polypeptide GalNAc-transferase gene family
journal, December 2011

In Defense of the Oral Cavity: Structure, Biosynthesis, and Function of Salivary Mucins
journal, October 1995

O-Glycosylation regulates polarized secretion by modulating Tango1 stability
journal, May 2014

  • Zhang, L.; Syed, Z. A.; van Dijk Hard, I.
  • Proceedings of the National Academy of Sciences, Vol. 111, Issue 20
  • DOI: 10.1073/pnas.1322264111

The secretory proteins of the larval salivary gland of Drosophila melanogaster: Cytogenetic correlation of a protein and a puff
journal, February 1980

  • Velissariou, Voula; Ashburner, Michael
  • Chromosoma, Vol. 77, Issue 1
  • DOI: 10.1007/BF00292038

Altered O-glycosylation profile of MUC2 mucin occurs in active ulcerative colitis and is associated with increased inflammation
journal, January 2011

  • Larsson, Jessica M. Holmn; Karlsson, Hasse; Crespo, Jessica Gråberg
  • Inflammatory Bowel Diseases, Vol. 17, Issue 11
  • DOI: 10.1002/ibd.21625

Orchestrated content release from Drosophila glue-protein vesicles by a contractile actomyosin network
journal, December 2015

  • Rousso, Tal; Schejter, Eyal D.; Shilo, Ben-Zion
  • Nature Cell Biology, Vol. 18, Issue 2
  • DOI: 10.1038/ncb3288

Dissecting the Biological Role of Mucin-type O -Glycosylation Using RNA Interference in Drosophila Cell Culture
journal, August 2010

  • Zhang, Liping; Hagen, Kelly G. Ten
  • Journal of Biological Chemistry, Vol. 285, Issue 45
  • DOI: 10.1074/jbc.M110.133561

Secretory granule biogenesis: rafting to the SNARE
journal, March 2001

Multiple Members of the UDP-GalNAc: Polypeptide N -Acetylgalactosaminyltransferase Family Are Essential for Viability in Drosophila
journal, December 2011

  • Tran, Duy T.; Zhang, Liping; Zhang, Ying
  • Journal of Biological Chemistry, Vol. 287, Issue 8
  • DOI: 10.1074/jbc.M111.306159

Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation
journal, May 2015

  • Lira-Navarrete, Erandi; de las Rivas, Matilde; Compañón, Ismael
  • Nature Communications, Vol. 6, Issue 1
  • DOI: 10.1038/ncomms7937

Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome
journal, February 2004

  • Parks, Annette L.; Cook, Kevin R.; Belvin, Marcia
  • Nature Genetics, Vol. 36, Issue 3
  • DOI: 10.1038/ng1312

The carbohydrate-active enzymes database (CAZy) in 2013
journal, November 2013

  • Lombard, Vincent; Golaconda Ramulu, Hemalatha; Drula, Elodie
  • Nucleic Acids Research, Vol. 42, Issue D1
  • DOI: 10.1093/nar/gkt1178

Secretory Granule Exocytosis
journal, April 2003

AP-1 and clathrin are essential for secretory granule biogenesis in Drosophila
journal, June 2011

  • Burgess, Jason; Jauregui, Miluska; Tan, Julie
  • Molecular Biology of the Cell, Vol. 22, Issue 12
  • DOI: 10.1091/mbc.e11-01-0054

Inactivating germ-line and somatic mutations in polypeptide N-acetylgalactosaminyltransferase 12 in human colon cancers
journal, July 2009

  • Guda, K.; Moinova, H.; He, J.
  • Proceedings of the National Academy of Sciences, Vol. 106, Issue 31
  • DOI: 10.1073/pnas.0901454106

Features and development of Coot
journal, March 2010

  • Emsley, P.; Lohkamp, B.; Scott, W. G.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
  • DOI: 10.1107/S0907444910007493

The Diversity of O -Linked Glycans Expressed during Drosophila melanogaster Development Reflects Stage- and Tissue-specific Requirements for Cell Signaling
journal, August 2008

  • Aoki, Kazuhiro; Porterfield, Mindy; Lee, Samuel S.
  • Journal of Biological Chemistry, Vol. 283, Issue 44
  • DOI: 10.1074/jbc.M804925200

Drosophila Sgs genes: Stage and tissue specificity of hormone responsiveness
journal, January 1996

A graphical user interface to the CCP 4 program suite
journal, June 2003

  • Potterton, Elizabeth; Briggs, Peter; Turkenburg, Maria
  • Acta Crystallographica Section D Biological Crystallography, Vol. 59, Issue 7
  • DOI: 10.1107/S0907444903008126

PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

Structural Insight into the Stabilizing Effect of O-Glycosylation
journal, May 2017

The N Terminus of the MUC2 Mucin Forms Trimers That Are Held Together within a Trypsin-resistant Core Fragment
journal, October 2002

  • Godl, Klaus; Johansson, Malin E. V.; Lidell, Martin E.
  • Journal of Biological Chemistry, Vol. 277, Issue 49
  • DOI: 10.1074/jbc.M208483200

A UDP-GalNAc:Polypeptide N -Acetylgalactosaminyltransferase Is Essential for Viability in Drosophila melanogaster
journal, March 2002

  • Hagen, Kelly G. Ten; Tran, Duy T.
  • Journal of Biological Chemistry, Vol. 277, Issue 25
  • DOI: 10.1074/jbc.M201807200

Real-time insights into regulated exocytosis
journal, March 2017

  • Tran, Duy T.; Ten Hagen, Kelly G.
  • Journal of Cell Science, Vol. 130, Issue 8
  • DOI: 10.1242/jcs.193425

Advances in understanding glycosyltransferases from a structural perspective
journal, October 2014

Insulin secretion in health and disease: genomics, proteomics and single vesicle dynamics
journal, March 2006

  • Rutter, G. A.; Varadi, A.; Tsuboi, T.
  • Biochemical Society Transactions, Vol. 34, Issue 2
  • DOI: 10.1042/BST0340247

Feedback inhibition of actin on Rho mediates content release from large secretory vesicles
journal, March 2018

  • Segal, Dagan; Zaritsky, Assaf; Schejter, Eyal D.
  • The Journal of Cell Biology, Vol. 217, Issue 5
  • DOI: 10.1083/jcb.201711006

Dynamic Association between the Catalytic and Lectin Domains of Human UDP-GalNAc:Polypeptide α- N -Acetylgalactosaminyltransferase-2
journal, January 2006

  • Fritz, Timothy A.; Raman, Jayalakshmi; Tabak, Lawrence A.
  • Journal of Biological Chemistry, Vol. 281, Issue 13
  • DOI: 10.1074/jbc.M513590200

Functional Characterization and Expression Analysis of Members of the UDP-GalNAc:Polypeptide N- Acetylgalactosaminyltransferase Family from Drosophila melanogaster
journal, June 2003

  • Ten Hagen, Kelly G.; Tran, Duy T.; Gerken, Thomas A.
  • Journal of Biological Chemistry, Vol. 278, Issue 37
  • DOI: 10.1074/jbc.M303836200

Multiple roles for the actin cytoskeleton during regulated exocytosis
journal, September 2012

  • Porat-Shliom, Natalie; Milberg, Oleg; Masedunskas, Andrius
  • Cellular and Molecular Life Sciences, Vol. 70, Issue 12
  • DOI: 10.1007/s00018-012-1156-5

HID-1 is required for homotypic fusion of immature secretory granules during maturation
journal, October 2016

Calcium and pH-dependent packing and release of the gel-forming MUC2 mucin
journal, March 2012

  • Ambort, D.; Johansson, M. E. V.; Gustafsson, J. K.
  • Proceedings of the National Academy of Sciences, Vol. 109, Issue 15
  • DOI: 10.1073/pnas.1120269109

Role of salivary mucins in the protection of the oral cavity
journal, January 1982