Wayne I Lencer

Summary

Publications

  1. ncbi request reprint A passionate kiss, then run: exocytosis and recycling of IgG by FcRn
    Wayne I Lencer
    GI Cell Biology, Division of Pediatric Gastroenterology and Nutrition, Children s Hospital, Boston, MA 02115, USA
    Trends Cell Biol 15:5-9. 2005
  2. pmc Dependence of antibody-mediated presentation of antigen on FcRn
    Shuo Wang Qiao
    Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:9337-42. 2008
  3. pmc The immunologic functions of the neonatal Fc receptor for IgG
    Timo Rath
    Division of Gastroenterology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
    J Clin Immunol 33:S9-17. 2013
  4. pmc Neonatal Fc receptor for IgG (FcRn) regulates cross-presentation of IgG immune complexes by CD8-CD11b+ dendritic cells
    Kristi Baker
    Division of Gastroenterology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 108:9927-32. 2011
  5. pmc Ca2+-dependent calmodulin binding to FcRn affects immunoglobulin G transport in the transcytotic pathway
    Bonny L Dickinson
    The Research Institute for Children, Children s Hospital, Department of Pediatrics, New Orleans, LA 70118, USA
    Mol Biol Cell 19:414-23. 2008
  6. pmc Bidirectional transepithelial IgG transport by a strongly polarized basolateral membrane Fcgamma-receptor
    Steven M Claypool
    Harvard Medical School, Program in Immunology, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Mol Biol Cell 15:1746-59. 2004
  7. ncbi request reprint Human neonatal Fc receptor mediates transport of IgG into luminal secretions for delivery of antigens to mucosal dendritic cells
    Masaru Yoshida
    Gastroenterology Division, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    Immunity 20:769-83. 2004
  8. pmc Intoxication of zebrafish and mammalian cells by cholera toxin depends on the flotillin/reggie proteins but not Derlin-1 or -2
    David E Saslowsky
    Division of Gastroenterology, Children s Hospital, Boston, Massachusetts, USA
    J Clin Invest 120:4399-4409. 2010
  9. doi request reprint Immune and non-immune functions of the (not so) neonatal Fc receptor, FcRn
    Kristi Baker
    Division of Gastroenterology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Semin Immunopathol 31:223-36. 2009
  10. pmc Attenuated endocytosis and toxicity of a mutant cholera toxin with decreased ability to cluster ganglioside GM1 molecules
    Anne A Wolf
    GI Cell Biology, Enders 720, Children s Hospital Boston, 300 Longwood Ave, Boston, MA 02115, USA
    Infect Immun 76:1476-84. 2008

Collaborators

Detail Information

Publications49

  1. ncbi request reprint A passionate kiss, then run: exocytosis and recycling of IgG by FcRn
    Wayne I Lencer
    GI Cell Biology, Division of Pediatric Gastroenterology and Nutrition, Children s Hospital, Boston, MA 02115, USA
    Trends Cell Biol 15:5-9. 2005
    ..Similar to the process seen for neurotransmitter release at synaptic junctions, other vesicles fuse only partially, releasing FcRn-IgG complexes to mix into the plasma membrane in cycles of 3-4s over prolonged periods of time...
  2. pmc Dependence of antibody-mediated presentation of antigen on FcRn
    Shuo Wang Qiao
    Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:9337-42. 2008
    ....
  3. pmc The immunologic functions of the neonatal Fc receptor for IgG
    Timo Rath
    Division of Gastroenterology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
    J Clin Immunol 33:S9-17. 2013
    ..The increasing appreciation for FcRn in both homeostatic and pathological conditions is generating an intense interest in the potential for therapeutic modulation of FcRn binding to IgG and albumin...
  4. pmc Neonatal Fc receptor for IgG (FcRn) regulates cross-presentation of IgG immune complexes by CD8-CD11b+ dendritic cells
    Kristi Baker
    Division of Gastroenterology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 108:9927-32. 2011
    ..Given the centrality of FcRn in controlling cross-presentation, these studies lay the foundation for a unique means to therapeutically manipulate CD8(+) T-cell responses...
  5. pmc Ca2+-dependent calmodulin binding to FcRn affects immunoglobulin G transport in the transcytotic pathway
    Bonny L Dickinson
    The Research Institute for Children, Children s Hospital, Department of Pediatrics, New Orleans, LA 70118, USA
    Mol Biol Cell 19:414-23. 2008
    ..These results suggest a novel mechanism for regulation of IgG transport by calmodulin-dependent sorting of FcRn and its cargo away from a degradative pathway and into a bidirectional transcytotic route...
  6. pmc Bidirectional transepithelial IgG transport by a strongly polarized basolateral membrane Fcgamma-receptor
    Steven M Claypool
    Harvard Medical School, Program in Immunology, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Mol Biol Cell 15:1746-59. 2004
    ..Thus, the strong cell surface polarity displayed by hFcRn results from dominant basolateral sorting by motifs in the cytoplasmic tail that nonetheless allows for a cycle of bidirectional transcytosis...
  7. ncbi request reprint Human neonatal Fc receptor mediates transport of IgG into luminal secretions for delivery of antigens to mucosal dendritic cells
    Masaru Yoshida
    Gastroenterology Division, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    Immunity 20:769-83. 2004
    ..These results explain how IgG is secreted onto mucosal surfaces and scavenges luminal antigens for recognition by the immune system...
  8. pmc Intoxication of zebrafish and mammalian cells by cholera toxin depends on the flotillin/reggie proteins but not Derlin-1 or -2
    David E Saslowsky
    Division of Gastroenterology, Children s Hospital, Boston, Massachusetts, USA
    J Clin Invest 120:4399-4409. 2010
    ..These results revise current models for CT intoxication and implicate protein scaffolding of lipid rafts in the endo-somal sorting of the toxin-GM1 complex...
  9. doi request reprint Immune and non-immune functions of the (not so) neonatal Fc receptor, FcRn
    Kristi Baker
    Division of Gastroenterology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Semin Immunopathol 31:223-36. 2009
    ..A greater understanding of FcRn's pleiotropic roles is thus imperative for a variety of therapeutic purposes...
  10. pmc Attenuated endocytosis and toxicity of a mutant cholera toxin with decreased ability to cluster ganglioside GM1 molecules
    Anne A Wolf
    GI Cell Biology, Enders 720, Children s Hospital Boston, 300 Longwood Ave, Boston, MA 02115, USA
    Infect Immun 76:1476-84. 2008
    ....
  11. ncbi request reprint Raft trafficking of AB5 subunit bacterial toxins
    Wayne I Lencer
    GI Cell Biology, Enders 720, Children s Hospital Boston, the Harvard Digestive Diseases Center, and the Department of Pediatrics, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, USA
    Biochim Biophys Acta 1746:314-21. 2005
    ..The way certain lipids and proteins are clustered in the plane of the membrane to form lipid rafts likely explains how the glycolipids can function as sorting motifs for the toxins...
  12. pmc Cholera toxin: an intracellular journey into the cytosol by way of the endoplasmic reticulum
    Naomi L B Wernick
    GI Cell Biology, Children s Hospital and Harvard Medical School, Boston, MA, USA
    Toxins (Basel) 2:310-25. 2010
    ..Here, we review the mechanisms of toxin trafficking by GM1 and retro-translocation of the A1-chain to the cytosol...
  13. ncbi request reprint Role of p97 AAA-ATPase in the retrotranslocation of the cholera toxin A1 chain, a non-ubiquitinated substrate
    Michael Kothe
    GI Cell Biology, Children s Hospital Boston, the Harvard Digestive Diseases Center, Harvard Medical School, Massachusetts 02115, USA
    J Biol Chem 280:28127-32. 2005
    ..These results suggest that p97 does not provide the primary driving force for extracting the A1 chain from the endoplasmic reticulum, a finding that is consistent with a requirement for polyubiquitination in p97 function...
  14. pmc The recycling and transcytotic pathways for IgG transport by FcRn are distinct and display an inherent polarity
    Salit Tzaban
    Children s Hospital, Gastroenterology Division, Harvard Digestive Diseases Center, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 185:673-84. 2009
    ....
  15. pmc Retrograde transport of cholera toxin from the plasma membrane to the endoplasmic reticulum requires the trans-Golgi network but not the Golgi apparatus in Exo2-treated cells
    Yan Feng
    Department of Cell Biology, Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    EMBO Rep 5:596-601. 2004
    ..We propose that even in the absence of Exo2 the glycolipid pathway that carries the toxin from plasma membrane into the ER bypasses the Golgi apparatus entirely...
  16. pmc N-terminal extension of the cholera toxin A1-chain causes rapid degradation after retrotranslocation from endoplasmic reticulum to cytosol
    Naomi L B Wernick
    Gastrointestinal Cell Biology Laboratory, Children s Hospital, and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 285:6145-52. 2010
    ..Thus, retrotranslocation and refolding of the wild-type A1-chain must proceed in a way that protects these Lys residues from attack by E3 ligases...
  17. pmc Neonatal Fc receptor: from immunity to therapeutics
    Timothy T Kuo
    Division of Gastroenterology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA
    J Clin Immunol 30:777-89. 2010
    ..Here, we aim to summarize the basic understanding of FcRn biology, its functions in various organs, and the therapeutic design of antibody- and albumin-based therapeutics in light of their interactions with FcRn...
  18. pmc An FcRn-dependent role for anti-flagellin immunoglobulin G in pathogenesis of colitis in mice
    Kanna Kobayashi
    Gastroenterology Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Gastroenterology 137:1746-56.e1. 2009
    ....
  19. pmc Lipid sorting by ceramide structure from plasma membrane to ER for the cholera toxin receptor ganglioside GM1
    Daniel J F Chinnapen
    Division of Gastroenterology, Boston Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Dev Cell 23:573-86. 2012
    ..The results implicate a protein-dependent mechanism of lipid sorting by ceramide structure and provide a molecular explanation for the diversity and specificity of retrograde trafficking by CT in host cells...
  20. pmc Cross-presentation of IgG-containing immune complexes
    Kristi Baker
    Division of Gastroenterology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
    Cell Mol Life Sci 70:1319-34. 2013
    ....
  21. pmc Neonatal Fc receptor for IgG regulates mucosal immune responses to luminal bacteria
    Masaru Yoshida
    Department of Medicine, Brigham and Women s Hospital, and Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA
    J Clin Invest 116:2142-2151. 2006
    ....
  22. ncbi request reprint A biochemical method for tracking cholera toxin transport from plasma membrane to Golgi and endoplasmic reticulum
    Heidi E De Luca
    Gastrointestinal Cell Biology, Children s Hospital Boston, Harvard Medical School, Boston, MA, USA
    Methods Mol Biol 341:127-39. 2006
    ..This provides a biochemical readout for toxin entry into the trans Golgi (by 35S-sulfation) and ER (by N-glycosylation). In this chapter, we describe the methods we developed to study this trafficking pathway...
  23. pmc Gangliosides that associate with lipid rafts mediate transport of cholera and related toxins from the plasma membrane to endoplasmic reticulm
    Yukako Fujinaga
    GI Cell Biology, Children s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Biol Cell 14:4783-93. 2003
    ..Our results explain why LTIIb does not cause disease in humans and suggest that gangliosides with high affinity for lipid rafts may provide a general vehicle for the transport of toxins to the ER...
  24. pmc Cholera toxin toxicity does not require functional Arf6- and dynamin-dependent endocytic pathways
    Ramiro H Massol
    Department of Cell Biology, Harvard Medical School and The Center for Blood Research for Biomedical Research, Boston, Massachusetts 02115, USA
    Mol Biol Cell 15:3631-41. 2004
    ..These results are consistent with the existence of an additional retrograde pathway used by CT to reach the ER...
  25. pmc Ceramide activates JNK to inhibit a cAMP-gated K+ conductance and Cl- secretion in intestinal epithelia
    David E Saslowsky
    GI Cell Biology, Children s Hospital, and the Harvard Digestive Diseases Center, Boston, MA 02115, USA
    FASEB J 23:259-70. 2009
    ..These results define a novel lipid-mediated pathway for regulation of salt and water homeostasis at mucosal surfaces...
  26. pmc Rafting with cholera toxin: endocytosis and trafficking from plasma membrane to ER
    Daniel J F Chinnapen
    GI Cell Biology, Children s Hospital, Boston, MA 21115, USA
    FEMS Microbiol Lett 266:129-37. 2007
    ..GM1 is the vehicle that carries CT from PM to ER. Thus, the toxin pathway from PM to ER is a lipid-based sorting pathway, which is potentially meditated by the determinants of the GM1 ganglioside structure itself...
  27. ncbi request reprint The intracellular voyage of cholera toxin: going retro
    Wayne I Lencer
    GI Cell Biology, Children s Hospital and the Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Trends Biochem Sci 28:639-45. 2003
    ..Upon entering the cytosol, the A1-chain rapidly refolds, avoids the proteasome and induces toxicity...
  28. ncbi request reprint Retrograde transport of cholera toxin into the ER of host cells
    Wayne I Lencer
    GI Cell Biology, Children s Hospital Boston, Harvard Digestive Diseases Center, Department of Pediatrics Harvard Medical School, Boston, MA 02115, USA
    Int J Med Microbiol 293:491-4. 2004
    ..Here we discuss recent studies on the mechanism of transport from plasma membrane to the ER and on the reactions that unfold and retrotranslocate a portion of the toxin to the cytosol where toxicity is induced...
  29. pmc Receptor-mediated immunoglobulin G transport across mucosal barriers in adult life: functional expression of FcRn in the mammalian lung
    Gerburg M Spiekermann
    The Combined Program in Pediatric Gastroenterology and Nutrition, Children s Hospital, Boston, MA 02115, USA
    J Exp Med 196:303-10. 2002
    ..These data show that mucosal surfaces that express FcRn reabsorb IgG and explain a mechanism by which IgG may act in immune surveillance to retrieve lumenal antigens for processing in the lamina propria or systemically...
  30. pmc The heavy chain of neonatal Fc receptor for IgG is sequestered in endoplasmic reticulum by forming oligomers in the absence of beta2-microglobulin association
    Xiaoping Zhu
    Gastroenterology Division, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Biochem J 367:703-14. 2002
    ..The beta(2)m association with FcRn HC is critical for correct folding of FcRn and exiting the ER for routing to endosomes and the cell surface...
  31. ncbi request reprint Conversion of apical plasma membrane sphingomyelin to ceramide attenuates the intoxication of host cells by cholera toxin
    David E Saslowsky
    Children s Hospital, Harvard Digestive Diseases Center, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Cell Microbiol 10:67-80. 2008
    ..This result suggests that the cause for toxin resistance occurs at steps required for retro-translocation of the CT A1-chain to the cytosol...
  32. pmc How the controller is controlled - neonatal Fc receptor expression and immunoglobulin G homeostasis
    Shuo Wang Qiao
    Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Immunology 120:145-7. 2007
  33. pmc Functional reconstitution of human FcRn in Madin-Darby canine kidney cells requires co-expressed human beta 2-microglobulin
    Steven M Claypool
    Harvard Medical School, Program in Immunology, Gastroenterogy Division, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 277:28038-50. 2002
    ..These results show that human FcRn travels to the cell surface via the normal secretory pathway and that the appropriate expression and function of human FcRn in MDCK cells depends upon the co-expression of human beta(2)m...
  34. ncbi request reprint Diarrhea-associated HIV-1 APIs potentiate muscarinic activation of Cl- secretion by T84 cells via prolongation of cytosolic Ca2+ signaling
    Paul A Rufo
    GI Cell Biology, Combined Program in Pediatric Gastroenterology and Nutrition, Children s Hospital, 300 Longwood Ave, Boston, MA 02115, USA
    Am J Physiol Cell Physiol 286:C998-C1008. 2004
    ..These data show that APIs modulate Ca(2+) signaling in secretory epithelial cells and identify a novel target for treatment of clinically important API side effects...
  35. pmc The Cdc42 inhibitor secramine B prevents cAMP-induced K+ conductance in intestinal epithelial cells
    Henry E Pelish
    Department of Cell Biology and The CBR Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts, USA
    Biochem Pharmacol 71:1720-6. 2006
    ..These results suggest that Rho GTPases may be involved in the regulation of the chloride secretory response and identify secramine B an inhibitor of cAMP-dependent K+ conductance in intestinal epithelial cells...
  36. pmc Insights on the trafficking and retro-translocation of glycosphingolipid-binding bacterial toxins
    Jin A Cho
    Division of Gastroenterology and Nutrition, Department of Medicine, Children s Hospital Boston, Boston MA, USA Department of Pediatrics, Harvard Medical School, Boston, MA, USA
    Front Cell Infect Microbiol 2:51. 2012
    ..We also discuss several new studies that address the mechanisms of toxin unfolding in the ER and the mechanisms of CT A1-chain retro-translocation to the cytosol...
  37. pmc The unfolded protein response element IRE1α senses bacterial proteins invading the ER to activate RIG-I and innate immune signaling
    Jin A Cho
    Department of Medicine, Division of GI Cell Biology, Boston Children s Hospital, Boston, MA 02115, USA
    Cell Host Microbe 13:558-69. 2013
    ..We propose IRE1α provides for a generalized mechanism of innate immune surveillance originating within the ER lumen...
  38. pmc Multivalent immune complexes divert FcRn to lysosomes by exclusion from recycling sorting tubules
    Andrew W Weflen
    Division of Gastroenterology, Boston Children s Hospital, Boston, MA 02115 Department of Pediatrics, Harvard Medical School, Boston, MA 02115 Harvard Digestive Diseases Center, Boston, MA 02115 Division of Gastroenterology, Brigham and Women s Hospital, Boston, MA 02115 Department of Biomedical Science, University of Amsterdam, 1012 WX Amsterdam, Netherlands College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
    Mol Biol Cell 24:2398-405. 2013
    ..Thus physical properties of the lumenal ligand-receptor complex appear to act as key determinants for sorting between the recycling and lysosomal pathways by regulating FcRn entry into recycling tubules. ..
  39. pmc The zebrafish dag1 mutant: a novel genetic model for dystroglycanopathies
    Vandana Gupta
    Genomics Program and Division of Genetics, The Manton Center for Orphan Disease Research, Children s Hospital Boston, Boston, MA 02115, USA
    Hum Mol Genet 20:1712-25. 2011
    ....
  40. ncbi request reprint Signal transduction by bacterial proteins
    Wayne I Lencer
    Children s Hospital, Boston, Massachusetts, USA
    J Pediatr Gastroenterol Nutr 40:S33-4. 2005
  41. pmc Role of ubiquitination in retro-translocation of cholera toxin and escape of cytosolic degradation
    Chiara Rodighiero
    GI Cell Biology, Children s Hospital and Harvard Medical School, Boston, MA 02115, USA
    EMBO Rep 3:1222-7. 2002
    ....
  42. pmc Patching a leaky intestine
    Wayne I Lencer
    Department of Medicine, Children s Hospital Boston and Harvard Medical School, Boston, USA
    N Engl J Med 359:526-8. 2008
  43. ncbi request reprint Calnexin and ERp57 facilitate the assembly of the neonatal Fc receptor for IgG with beta 2-microglobulin in the endoplasmic reticulum
    Xiaoping Zhu
    Laboratory of Immunology, Virginia Maryland Regional College of Veterinary Medicine, University of Maryland, 8075 Greenmead Drive, College Park, MD 20742, USA
    J Immunol 175:967-76. 2005
    ..220 (tapasin-deficient) and 721.174 (TAP-deficient) cells transfected with FcRn. These findings show the importance of chaperones in FcRn assembly...
  44. ncbi request reprint Antibodies in the breakdown lane
    Richard S Blumberg
    Nat Biotechnol 23:1232-4. 2005
  45. pmc Distribution of the IgG Fc receptor, FcRn, in the human fetal intestine
    Uzma Shah
    Mucosal Immunology Laboratory, Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Charlestown, Massachusetts 02129 4404, USA
    Pediatr Res 53:295-301. 2003
    ....
  46. ncbi request reprint Trafficking of cholera toxin-ganglioside GM1 complex into Golgi and induction of toxicity depend on actin cytoskeleton
    Kamran Badizadegan
    Department of Pathology, Massachusetts General Hospital, Boston 02114, USA
    Am J Physiol Cell Physiol 287:C1453-62. 2004
    ....
  47. pmc Derlin-1 facilitates the retro-translocation of cholera toxin
    Kaleena M Bernardi
    Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Mol Biol Cell 19:877-84. 2008
    ..CTB may play a role in this process by targeting the holotoxin to Derlin-1, enabling the Derlin-1-bound PDI to unfold the A1 subunit and prepare it for transport...
  48. pmc Pulmonary delivery of an erythropoietin Fc fusion protein in non-human primates through an immunoglobulin transport pathway
    Alan J Bitonti
    Syntonix Pharmaceuticals, Incorporated, Waltham, MA 02451, USA
    Proc Natl Acad Sci U S A 101:9763-8. 2004
    ..c. in humans. These studies show that FcRn can be harnessed to noninvasively deliver bioactive proteins into the systemic circulation in therapeutic quantities...
  49. pmc Protein disulfide isomerase-like proteins play opposing roles during retrotranslocation
    Michele L Forster
    Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    J Cell Biol 173:853-9. 2006
    ..Thus, our data identify PDI family proteins that play opposing roles in ER quality control and establish an assay to further delineate the mechanism of CT retrotranslocation...