title: The NF-κB signaling protein Bcl10 regulates actin dynamics by controlling AP1 and OCRL-bearing vesicles.
abstract: The protein Bcl10 contributes to adaptive and innate immunity through the assembly of a signaling complex that plays a key role in antigen receptor and FcR-induced NF-κB activation. Here we demonstrate that Bcl10 has an NF-κB-independent role in actin and membrane remodeling downstream of FcR in human macrophages. Depletion of Bcl10 impaired Rac1 and PI3K activation and led to an abortive phagocytic cup rich in PI(4,5)P(2), Cdc42, and F-actin, which could be rescued with low doses of F-actin depolymerizing drugs. Unexpectedly, we found Bcl10 in a complex with the clathrin adaptors AP1 and EpsinR. In particular, Bcl10 was required to locally deliver the vesicular OCRL phosphatase that regulates PI(4,5)P(2) and F-actin turnover, both crucial for the completion of phagosome closure. Thus, we identify Bcl10 as an early coordinator of NF-κB-mediated immune response with endosomal trafficking and signaling to F-actin remodeling.
authors.affiliation: Inserm, U1016, Institut Cochin, Paris, France; CNRS, UMR 8104, Paris, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Marion
authors.forename: Julie
authors.initials: J
authors.lastname: Mazzolini
authors.forename: Floriane
authors.initials: F
authors.lastname: Herit
authors.forename: Pierre
authors.initials: P
authors.lastname: Bourdoncle
authors.forename: Nadège
authors.initials: N
authors.lastname: Kambou-Pene
authors.forename: Stephan
authors.initials: S
authors.lastname: Hailfinger
authors.forename: Martin
authors.initials: M
authors.lastname: Sachse
authors.forename: Jürgen
authors.initials: J
authors.lastname: Ruland
authors.forename: Alexandre
authors.initials: A
authors.lastname: Benmerah
authors.forename: Arnaud
authors.initials: A
authors.lastname: Echard
authors.forename: Margot
authors.initials: M
authors.lastname: Thome
authors.forename: Florence
authors.initials: F
authors.lastname: Niedergang
mesh_terms: D000199:Actins / Q000378:metabolism; D056704:Adaptive Immunity; D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000074018:B-Cell CLL-Lymphoma 10 Protein; D002460:Cell Line; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D010587:Phagocytosis; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011961:Receptors, Fc / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; C488088:Bcl10 protein, mouse; D016328:NF-kappa B; D009479:Neuropeptides; C107953:RAC1 protein, human; C484602:Rac1 protein, mouse; D011961:Receptors, Fc; D018808:Transcription Factor AP-1; D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human; C489581:Ocrl protein, mouse; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein