Autoantibodies to the Golgi complex are found primarily in patients with Sj?gren's syndrome and SLE although they are not restricted to these diseases. This competitive renewal application requests funding for the continuation of studies to characterize autoantigens of the Golgi complex and address the mechanisms that lead to the expression of autoantibodies to these intracellular organelle-associated proteins. The P.I.'s laboratory has been responsible for the identification of a family of Golgi antigens known as golgins. Common features of these autoantigens are that they are located on the cytoplasmic face of the Golgi cisternae and they have multiple alpha-helical coiled-coil rod domains flanked by non-coiled-coil and C- terminal domains. The goal of the proposed studies is to determine if the common structure and function for members of this protein family can explain the origin and production of autoantibodies in disease states.
Specific Aim 1 will examine common features of golgins that may explain why they are targets of human anti-Golgi autoantibodies. The P.I. will characterize the events associated with the Golgi complex and golgins and their stability during apoptosis and necrosis. Hypotheses on how these autoantibodies may be produced in experimental models will be examined.
Specific Aim 2 will examine if Golgi fragments and vesicular structures will induce immune and autoimmune response in experimental mice.
Specific Aim 3 will elucidate the target of Golgi complex in lactate dehydrogenase-elevating virus (LDV) infected mice and address mechanism of how autoimmune response to the Golgi complex can be produced in these mice. Earlier studies have shown that LDV infected mice produce anti-Golgi antibodies. Our current data suggest that the autoimmune response to cytoplasmic organelles such as the Golgi complex is uniquely different from other intracellular autoantigens examined to date. It is anticipated that testing of the P.I.'s hypotheses will provide new insights into autoimmunity and autoimmune diseases associated with subcellular organelles.
| Nozawa, Kazuhisa; Fritzler, Marvin J; Takasaki, Yoshinari et al. (2009) Co-clustering of Golgi complex and other cytoplasmic organelles to crescentic region of half-moon nuclei during apoptosis. Cell Biol Int 33:148-57 |
| Nozawa, Kazuhisa; Fritzler, Marvin J; Ikeda, Keigo et al. (2008) Differential anti-Golgi complex autoantibody production following murine lactate dehydrogenase-elevating virus infection. Immunopharmacol Immunotoxicol 30:13-25 |
| Yamasaki, Yoshioki; Narain, Sonali; Yoshida, Hideo et al. (2007) Autoantibodies to RNA helicase A: a new serologic marker of early lupus. Arthritis Rheum 56:596-604 |
| Yamasaki, Yoshioki; Narain, Sonali; Hernandez, Liza et al. (2006) Autoantibodies against the replication protein A complex in systemic lupus erythematosus and other autoimmune diseases. Arthritis Res Ther 8:R111 |
| Jakymiw, Andrew; Ikeda, Keigo; Fritzler, Marvin J et al. (2006) Autoimmune targeting of key components of RNA interference. Arthritis Res Ther 8:R87 |
| Lian, Shangli; Jakymiw, Andrew; Eystathioy, Theophany et al. (2006) GW bodies, microRNAs and the cell cycle. Cell Cycle 5:242-5 |
| Jakymiw, Andrew; Lian, Shangli; Eystathioy, Theophany et al. (2005) Disruption of GW bodies impairs mammalian RNA interference. Nat Cell Biol 7:1267-74 |
| Lu, Yu; Ye, Ping; Chen, Shun-le et al. (2005) Identification of kinectin as a novel Behcet's disease autoantigen. Arthritis Res Ther 7:R1133-9 |
| Nozawa, Kazuhisa; Fritzler, Marvin J; Chan, Edward K L (2005) Unique and shared features of Golgi complex autoantigens. Autoimmun Rev 4:35-41 |
| Nozawa, Kazuhisa; Fritzler, Marvin J; von Muhlen, Carlos A et al. (2004) Giantin is the major Golgi autoantigen in human anti-Golgi complex sera. Arthritis Res Ther 6:R95-102 |
Showing the most recent 10 out of 22 publications
