HS1-associated protein X-1 interacts with membrane-bound IgE: impact on receptor-mediated internalization.
Engagement of the BCR triggers signals that control affinity maturation, memory induction, differentiation, and various other physiological processes in B cells. In previous work, we showed that truncation of the cytoplasmic tail of membrane-bound Ig (mIg)E in vivo resulted in lower serum IgE levels, decreased numbers of IgE-secreting plasma cells, and the abrogation of specific secondary responses correlating with a defect in the selection of high-affinity Abs during the germinal center reaction. We concluded that the Ag receptor is necessary at all times during Ab responses not only for the maturation process, but also for the expansion of Ag-specific B cells. Based on these results, we asked whether the cytoplasmic tail of mIgE, or specific proteins binding the cytoplasmic tail in vivo commit a signal transduction accompanying the B cell along its differentiation process. In this study, we present the identification of HS1-associated protein X-1 as a novel protein interacting with the cytoplasmic tail of mIgE. ELISA, surface plasmon resonance analysis, and coimmunoprecipitation experiments confirmed the specific interaction in vitro. In functional assays, we clearly showed that HS1-associated protein X-1 expression levels influence the efficiency of BCR-mediated Ag internalization.
Oberndorfer
Iris
I
Department of Molecular Biology, University of Salzburg, Hellbrunnerstrasse 34, A-5020 Salzburg, Austria.
Schmid
Doris
D
Geisberger
Roland
R
Achatz-Straussberger
Gertrude
G
Crameri
Reto
R
Lamers
Marinus
M
Achatz
Gernot
G
D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity; D001435:Bacteriophages / Q000235:genetics; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000276:immunology* / Q000378:metabolism*; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000378:metabolism*; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D025941:Protein Interaction Mapping; D011506:Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism
C491295:Hs1bp1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D011506:Proteins; D034741:RNA, Small Interfering; D011947:Receptors, Antigen, B-Cell; D011994:Recombinant Proteins; D007073:Immunoglobulin E