The tetraspanin CD81 is necessary for partitioning of coligated CD19/CD21-B cell antigen receptor complexes into signaling-active lipid rafts.
Tetraspanins have been hypothesized to facilitate the organization of functional multimolecular membrane complexes. In B cells the tetraspanin CD81 is a component of the CD19/CD21 complex. When coligated to the B cell Ag receptor (BCR), the CD19/CD21 complex significantly enhances BCR signaling in part by prolonging the association of the BCR with signaling-active lipid rafts. In this study CD81 is shown to associate with lipid rafts upon coligation of the BCR and the CD19/CD21 complex. Using B cells from CD81-deficient mice we demonstrate that in the absence of CD81, coligated BCR and CD19/CD21 complexes fail to partition into lipid rafts and enhance BCR signaling from rafts. Furthermore, a chimeric CD19 protein that associates only weakly if at all with CD81 fails to promote the association of coligated BCR with lipid rafts. The requirement for CD81 to promote lipid raft association may define a novel mechanism by which tetraspanins function as molecular facilitators of signaling receptors.
Cherukuri
Anu
A
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Twinbrook II, 12441 Parklawn Drive, Rockville, MD 20852, USA.
Shoham
Tsipi
T
Sohn
Hae Won
HW
Levy
Shoshana
S
Brooks
Stephen
S
Carter
Robert
R
Pierce
Susan K
SK
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D018941:Antigens, CD19 / Q000378:metabolism* / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D002461:Cell Line, Transformed; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005260:Female; D008024:Ligands; D008297:Male; D021962:Membrane Microdomains / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism* / Q000502:physiology; D017464:Receptors, Complement 3d / Q000378:metabolism* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D060225:Tetraspanin 28; D059470:Tetraspanins
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D018941:Antigens, CD19; C554799:Cd81 protein, mouse; D008024:Ligands; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011947:Receptors, Antigen, B-Cell; D017464:Receptors, Complement 3d; D011993:Recombinant Fusion Proteins; D060225:Tetraspanin 28; D059470:Tetraspanins; C512651:Tspan2 protein, mouse