We are interested in the recognition and transport of antibodies by Fc receptors. Using a combination of X-ray crystallography, biochemistry, electron tomography, and confocal fluorescent microscopy, we have been investigating the neonatal Fc receptor (FcRn) and its interactions with IgG, focusing on defining the pathway by which FcRn-IgG and/or FcRn-Fc complexes are transported in intracellular endosomes across epithelial cell barriers. We now seek to build upon our initial electron tomography results, which defined the pathway of FcRn-mediated transcytosis across intestinal epithelial cells, by combining electron tomography, which allows 3D imaging of cells, with live cell fluorescent imaging, which can be used for 4D studies (3D plus time). Many of the Fc receptors for which we have high-resolution X-ray structures also transport antibodies through endosomes, therefore we plan to extend our imaging studies to other Fc receptor systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI041239-15
Application #
8423072
Study Section
Special Emphasis Panel (NSS)
Program Officer
Prabhudas, Mercy R
Project Start
1997-04-01
Project End
2013-12-31
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
15
Fiscal Year
2013
Total Cost
$385,939
Indirect Cost
$147,705
Name
California Institute of Technology
Department
None
Type
Schools of Arts and Sciences
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125
Ndjamen, Blaise; Farley, Alexander H; Lee, Terri et al. (2014) The herpes virus Fc receptor gE-gI mediates antibody bipolar bridging to clear viral antigens from the cell surface. PLoS Pathog 10:e1003961
Gan, Lu; Ladinsky, Mark S; Jensen, Grant J (2013) Chromatin in a marine picoeukaryote is a disordered assemblage of nucleosomes. Chromosoma 122:377-86
Wu, Yunji; West Jr, Anthony P; Kim, Helen J et al. (2013) Structural basis for enhanced HIV-1 neutralization by a dimeric immunoglobulin G form of the glycan-recognizing antibody 2G12. Cell Rep 5:1443-55
Gan, Lu; Ladinsky, Mark S; Jensen, Grant J (2011) Organization of the smallest eukaryotic spindle. Curr Biol 21:1578-83
He, Yongning; Bjorkman, Pamela J (2011) Structure of FcRY, an avian immunoglobulin receptor related to mammalian mannose receptors, and its complex with IgY. Proc Natl Acad Sci U S A 108:12431-6
Bai, Yu; Ye, Lilin; Tesar, Devin B et al. (2011) Intracellular neutralization of viral infection in polarized epithelial cells by neonatal Fc receptor (FcRn)-mediated IgG transport. Proc Natl Acad Sci U S A 108:18406-11
Jerdeva, Galina V; Tesar, Devin B; Huey-Tubman, Kathryn E et al. (2010) Comparison of FcRn- and pIgR-Mediated Transport in MDCK Cells by Fluorescence Confocal Microscopy. Traffic :
Tesar, Devin B; Bjorkman, Pamela J (2010) An intracellular traffic jam: Fc receptor-mediated transport of immunoglobulin G. Curr Opin Struct Biol 20:226-33
He, Yongning; Jensen, Grant J; Bjorkman, Pamela J (2009) Nanogold as a specific marker for electron cryotomography. Microsc Microanal 15:183-8
Tesar, Devin B; Cheung, Evelyn J; Bjorkman, Pamela J (2008) The chicken yolk sac IgY receptor, a mammalian mannose receptor family member, transcytoses IgY across polarized epithelial cells. Mol Biol Cell 19:1587-93

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