Epithelial cells lining exposed mucosal surfaces, such as the gastrointestinal, respiratory, and genito-urinary tracts, express the polymeric immunoglobulin receptor (plgR). The plgR binds to IgA at the basolateral surface of the epithelial cell. The plgR-IgA complex is endocytosed, transcytosed, and the IgA is released at the apical surface of the cell. The IgA discharged into secretions forms the first immunological defense against mucosal infections, which account for >95% of human infectious diseases. Mucosal infections include many high priority diseases, such as AIDS and AIDS-associated infections, emerging and re-emerging diseases such TB and multiple antibiotic resistant bacteria, and biological warfare/terrorist agents (including inhalational anthrax). Moreover, it was recently discovered that as the IgA is being transcytosed across the cell, it can neutralize viruses within the cell, and that this is a major mechanism of antiviral immunity. Also, the major bacterial pathogen, 5. pneumoniae, uses the plgR to enter and transcytose across nasopharyngeal cells, leading to disseminated infection. The most effective strategy for control of mucosal infections is mucosal vaccination. The goal of this research is to understand the molecular mechanism of transcytosis of IgA. This is crucial to understanding the mucosal immune response and the development of mucosal vaccines. The role of syntaxins in targeting movement of plgR specifically to the apical and basolateral surfaces of epithelial cells will be analyzed. The role of the mammalian retromer complex in trafficking of the plgR will be determined. The mechanism by which the recently discovered GGA3 protein directs plgR traffic will be dissected.
| Cerruti, Benedetta; Puliafito, Alberto; Shewan, Annette M et al. (2013) Polarity, cell division, and out-of-equilibrium dynamics control the growth of epithelial structures. J Cell Biol 203:359-72 |
| Roignot, Julie; Peng, Xiao; Mostov, Keith (2013) Polarity in mammalian epithelial morphogenesis. Cold Spring Harb Perspect Biol 5: |
| Cai, Liang; Mostov, Keith E (2012) Cell height: Tao rising. J Cell Biol 199:1023-4 |
| Roland, Joseph T; Bryant, David M; Datta, Anirban et al. (2011) Rab GTPase-Myo5B complexes control membrane recycling and epithelial polarization. Proc Natl Acad Sci U S A 108:2789-94 |
| Shewan, Annette; Eastburn, Dennis J; Mostov, Keith (2011) Phosphoinositides in cell architecture. Cold Spring Harb Perspect Biol 3:a004796 |
| Eastburn, Dennis J; Mostov, Keith E (2010) Laying the foundation for epithelia: insights into polarized basement membrane deposition. EMBO Rep 11:329-30 |
| Cai, Liang; Mostov, Keith (2009) Polarity is destiny. Cell 139:660-2 |
| Luton, Frédéric; Hexham, Mark J; Zhang, Min et al. (2009) Identification of a cytoplasmic signal for apical transcytosis. Traffic 10:1128-42 |
| Bryant, David M; Mostov, Keith E (2008) From cells to organs: building polarized tissue. Nat Rev Mol Cell Biol 9:887-901 |
| Zegers, Mirjam M P; O'Brien, Lucy E; Yu, Wei et al. (2003) Epithelial polarity and tubulogenesis in vitro. Trends Cell Biol 13:169-76 |
Showing the most recent 10 out of 31 publications
