Rafts and synapses in the spatial organization of immune cell signaling receptors.
The multichain immune recognition receptors (MIRRs), including the T cell and B cell antigen receptors and the high affinity receptor for IgE, play an important role in immune cell signaling. The MIRRs have no inherent kinase activity, but rather associate with members of the Src-family kinases to initiate signaling. Although a great deal is understood about the biochemical cascades triggered by MIRRs, the mechanism by which signaling is initiated was not known. The evidence now indicates that the Src-family kinases are concentrated in cholesterol- and sphingolipid-rich membrane microdomains, termed lipid rafts, that exclude the MIRRs. Upon ligand-induced crosslinking the MIRRs translocate into rafts where they are phosphorylated. The MIRRs subsequently form highly ordered, polarized structures termed immunological synapses that provide for prolonged signaling. An understanding of the biochemical composition of rafts and synapses and the mechanisms by which these form should lend insight into the regulation of immune cell activation.
Dykstra
M
M
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.
Cherukuri
A
A
Pierce
S K
SK
D020816:Amino Acid Motifs; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology; D001427:Bacterial Toxins / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology; D000071178:CD48 Antigen; D002454:Cell Differentiation; D002784:Cholesterol / Q000032:analysis; D006028:Glycosphingolipids / Q000032:analysis; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D007152:Immunologic Capping; D008024:Ligands; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008563:Membrane Lipids / Q000032:analysis; D021962:Membrane Microdomains / Q000737:chemistry / Q000201:enzymology / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011940:Receptor Aggregation; D017464:Receptors, Complement 3d / Q000276:immunology; D011971:Receptors, Immunologic / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013107:Sphingolipids / Q000032:analysis; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D014763:Viral Matrix Proteins / Q000502:physiology; D019061:src-Family Kinases / Q000502:physiology
D015703:Antigens, CD; D018941:Antigens, CD19; D001427:Bacterial Toxins; D018106:CD28 Antigens; D000071178:CD48 Antigen; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D006028:Glycosphingolipids; D008024:Ligands; D046911:Macromolecular Substances; D008563:Membrane Lipids; D017464:Receptors, Complement 3d; D011971:Receptors, Immunologic; D013107:Sphingolipids; D014763:Viral Matrix Proteins; D002784:Cholesterol; D019061:src-Family Kinases; D011493:Protein Kinase C