Indications for a protective function of beta2-glycoprotein I in thrombotic thrombocytopenic purpura.

It has been shown that ß(2) -glycoprotein I (ß(2) GPI) interacts with von Willebrand factor (VWF) in a glycoprotein (GP)Ib binding state. Given the presence of active VWF multimers in thrombotic thrombocytopenic purpura (TTP), we speculated that ß(2) GPI might play a role in TTP. We found that ß(2) GPI plasma levels were significantly lower in acute and remission TTP patients than in normal controls, showing a direct correlation with ADAMTS 13 levels and an inverse correlation with the extent of VWF activation. In vitro flow experiments demonstrated that ß(2) GPI can block platelet adhesion to endothelial cell-derived VWF strings. We confirmed the direct binding of ß(2) GPI to VWF by surface plasmon resonance, and determined that domain I of ß(2) GPI is the binding site of VWF A1 domain. Adhesion of ß(2) GPI to erythrocytes and platelets was increased in the presence of active VWF, indicating that ß(2) GPI may be cleared from the circulation during TTP episodes together with blood cells. Our findings suggest that ß(2) GPI may protect from the effects of hyper-functional VWF by inhibiting its interaction with platelets.

Expression and functional analyses of EXO70 genes in Arabidopsis implicate their roles in regulating cell type-specific exocytosis.

During exocytosis, Golgi-derived vesicles are tethered to the target plasma membrane by a conserved octameric complex called the exocyst. In contrast to a single gene in yeast and most animals, plants have greatly increased number of EXO70 genes in their genomes, with functions very much unknown. Reverse transcription-polymerase chain reactions were performed on all 23 EXO70 genes in Arabidopsis (Arabidopsis thaliana) to examine their expression at the organ level. Cell-level expression analyses were performed using transgenic plants carrying ß-glucuronidase reporter constructs, showing that EXO70 genes are primarily expressed in potential exocytosis-active cells such as tip-growing and elongating cells, developing xylem elements, and guard cells, whereas no expression was observed in cells of mature organs such as well-developed leaves, stems, sepals, and petals. Six EXO70 genes are expressed in distinct but partially overlapping stages during microspore development and pollen germination. A mutation in one of these genes, EXO70C1 (At5g13150), led to retarded pollen tube growth and compromised male transmission. This study implies that multiplications of EXO70 genes may allow plants to acquire cell type- and/or cargo-specific regulatory machinery for exocytosis.