BCMA signaling from the Golgi apparatus in B cells
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B-cell maturation antigen (BCMA) targeting gained a rapid approval for multiple myeloma, and is currently investigated in B-cell lymphomas. Here, we report that the trans Golgi network (TGN) retained BCMA due to a motif in its transmembrane/cytoplasmic domain in diffuse large B-cell lymphomas (DLBCL). To achieve signaling, one of its ligands, a proliferation inducing ligand (APRIL), bound to surface heparan sulfate proteoglycans (HSPGs), got endocytosed by the calveolin pathway and trafficked to the TGN via the retrograde route. In the TGN, APRIL/BCMA interactions activated the NF-κB pathway. BCMA ubiquitination followed by proteosomal degradation mediated signal termination. Growth impairment of DLBCL xenografts in APRIL -deficient animals confirmed the in vivo activity of TGN BCMA. Our study constitutes the first description for a signal activity from the Golgi apparatus among the TNF receptor family.
