The architecture of IgE-dependent mast cell signaling - A complex story
Por:
Rivera J., Gonzalez-Espinosa C., Kovarova M., Parravicini V.
Publicada:
1 ene 2002
Resumen:
Background: Activation of a mast cell is a common consequence of the interaction of an allergen with receptor-bound IgE that causes these receptors to aggregate, and couples them to a complex series of intracellular biochemical events that govern the cells' response. In this article we summarize our view of this process. Method/data base: Molecular genetic manipulations, biochemical assays, and confocal microscopy are the major techniques used in these studies. Results: Allergen-aggregation of immunoglobulin E (IgE) receptors on mast cells causes the assembly of signaling molecules into macromolecular complexes whose constituents are determined by the proteins that are expressed in a given microenvironment. Aggregated receptors move into specialized plasma membrane domains that are enriched in glycosphingolipids and cholesterol (lipid rafts). These domains seem to serve in signal amplification by sequestering proteins such as the linker for activation of T cells (LAT) that scaffold the assembly of signaling molecules into macromolecular complexes. Whereas some of these signaling complexes are formed in lipid rafts, others can be found in non-lipid-raft membranes and in the cytoplasm. The generation of signals from these macromolecular complexes is facilitated by the cell's cytoskeleton and is regulated by the extent of receptor occupancy and the affinity of the allergen, both of which influence the size and/or stability of receptor aggregates. Conclusion: Understanding how the diverse signals generated by these complexes are integrated in regulating a mast cell's effector response requires at least partial resolution before the potential clinical benefits from predicting mast cell behavior can be realized.
Filiaciones:
Rivera J.:
Molecular Inflammatory Section, Natl. Inst. Arthritis/Musculoskel., 10 Center Drive, Bethesda, MD 20892-1820, United States
Gonzalez-Espinosa C.:
Molecular Inflammatory Section, Natl. Inst. Arthritis/Musculoskel., 10 Center Drive, Bethesda, MD 20892-1820, United States
Kovarova M.:
Molecular Inflammatory Section, Natl. Inst. Arthritis/Musculoskel., 10 Center Drive, Bethesda, MD 20892-1820, United States
Parravicini V.:
Molecular Inflammatory Section, Natl. Inst. Arthritis/Musculoskel., 10 Center Drive, Bethesda, MD 20892-1820, United States
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