Identification of proteoglycans as the APRIL-specific binding partners.

Details

Ressource 1Download: BIB_2EEA140949C2.P001.pdf (964.40 [Ko])
State: Public
Version: author
Serval ID
serval:BIB_2EEA140949C2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification of proteoglycans as the APRIL-specific binding partners.
Journal
Journal of Experimental Medicine
Author(s)
Ingold K., Zumsteg A., Tardivel A., Huard B., Steiner Q.G., Cachero T.G., Qiang F., Gorelik L., Kalled S.L., Acha-Orbea H., Rennert P.D., Tschopp J., Schneider P.
ISSN
0022-1007 (Print)
ISSN-L
0022-1007
Publication state
Published
Issued date
2005
Volume
201
Number
9
Pages
1375-1383
Language
english
Abstract
B cell activating factor of the tumor necrosis factor (TNF) family (BAFF) and a proliferation-inducing ligand (APRIL) are closely related ligands within the TNF superfamily that play important roles in B lymphocyte biology. Both ligands share two receptors--transmembrane activator and calcium signal--modulating cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA)--that are predominantly expressed on B cells. In addition, BAFF specifically binds BAFF receptor, whereas the nature of a postulated APRIL-specific receptor remains elusive. We show that the TNF homology domain of APRIL binds BCMA and TACI, whereas a basic amino acid sequence (QKQKKQ) close to the NH2 terminus of the mature protein is required for binding to the APRIL-specific "receptor." This interactor was identified as negatively charged sulfated glycosaminoglycan side chains of proteoglycans. Although T cell lines bound little APRIL, the ectopic expression of glycosaminoglycan-rich syndecans or glypicans conferred on these cells a high binding capacity that was completely dependent on APRIL's basic sequence. Moreover, syndecan-1-positive plasma cells and proteoglycan-rich nonhematopoietic cells displayed high specific, heparin-sensitive binding to APRIL. Inhibition of BAFF and APRIL, but not BAFF alone, prevented the survival and/or the migration of newly formed plasma cells to the bone marrow. In addition, costimulation of B cell proliferation by APRIL was only effective upon APRIL oligomerization. Therefore, we propose a model whereby APRIL binding to the extracellular matrix or to proteoglycan-positive cells induces APRIL oligomerization, which is the prerequisite for the triggering of TACI- and/or BCMA-mediated activation, migration, or survival signals.
Keywords
Animals, B-Cell Activating Factor, B-Cell Activation Factor Receptor, B-Cell Maturation Antigen, B-Lymphocytes/metabolism, Cell Line, Cell Movement/genetics, Cell Proliferation, Flow Cytometry, Heparin/metabolism, Humans, Immunoprecipitation, Membrane Proteins/metabolism, Mice, Models, Biological, Nuclear Proteins/metabolism, Plasma Cells/metabolism, Protein Binding, Protein Structure, Tertiary, Proteoglycans/metabolism, Receptors, Tumor Necrosis Factor/metabolism, Transfection, Transmembrane Activator and CAML Interactor Protein, Tumor Necrosis Factor-alpha/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 14:48
Last modification date
20/08/2019 13:13
Usage data