The orderly transport of proteins within the secretory pathway of eucaryotic cells is mediated by the specific recognition and fusion of transport vesicles with distinct target organelle-associated membrane proteins termed SNAREs. In our attempt to understand protein trafficking in lymphocytes, we have cloned novel SNAREs or SNARE- related proteins. Using the yeast two-hybrid system, we have isolated the cDNA for SNAP-23, a ubiquitously expressed membrane-associated protein involved in facilitating vesicle docking and fusion with the plasma membrane. We have also identified the novel kinase SNAK that phosphorylates SNAP-23 and regulates its association with syntaxin, another membrane trafficking protein. In addition, we have identified a novel syntaxin that localizes to late endosomes and are investigating the function of this protein in lymphocyte biology.We are also investigating the role of post-translational modifications in the transport of MHC class II molecules to antigen processing compartments. We have identified the phosphorylation sites on the MHC class II- associated invariant chain, have identifed protein kinase C as the kinase responsible for invariant chain phosphorylation, and are investigating the possibility that invariant chain phosphorylation enhances antigen presentation during the immune response. - antigen presentation, B lymphocytes, major histocompatibility complex class II, protein phosphorylation, protein transport,

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC009404-05
Application #
6289272
Study Section
Special Emphasis Panel (EIB)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Anderson, Howard A; Roche, Paul A (2015) MHC class II association with lipid rafts on the antigen presenting cell surface. Biochim Biophys Acta 1853:775-80
Berger, Adam C; Roche, Paul A (2009) MHC class II transport at a glance. J Cell Sci 122:1-4
Bryceson, Yenan T; Rudd, Eva; Zheng, Chengyun et al. (2007) Defective cytotoxic lymphocyte degranulation in syntaxin-11 deficient familial hemophagocytic lymphohistiocytosis 4 (FHL4) patients. Blood 110:1906-15
Muntasell, Aura; Berger, Adam C; Roche, Paul A (2007) T cell-induced secretion of MHC class II-peptide complexes on B cell exosomes. EMBO J 26:4263-72
Puri, Niti; Roche, Paul A (2006) Ternary SNARE complexes are enriched in lipid rafts during mast cell exocytosis. Traffic 7:1482-94
Roche, Paul A (2006) Gold-plating MHC class II molecules. Nat Chem Biol 2:178-9
Poloso, Neil J; Muntasell, Aura; Roche, Paul A (2004) MHC class II molecules traffic into lipid rafts during intracellular transport. J Immunol 173:4539-46
Poloso, Neil J; Roche, Paul A (2004) Association of MHC class II-peptide complexes with plasma membrane lipid microdomains. Curr Opin Immunol 16:103-7
Hiltbold, Elizabeth M; Poloso, Neil J; Roche, Paul A (2003) MHC class II-peptide complexes and APC lipid rafts accumulate at the immunological synapse. J Immunol 170:1329-38
Puri, Niti; Kruhlak, Michael J; Whiteheart, Sidney W et al. (2003) Mast cell degranulation requires N-ethylmaleimide-sensitive factor-mediated SNARE disassembly. J Immunol 171:5345-52

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