The NF-κB Signaling Protein Bcl10 Regulates Actin Dynamics by Controlling AP1 and OCRL-Bearing Vesicles

CNRS, UMR 8104, Paris, France
Developmental Cell (Impact Factor: 9.71). 11/2012; 23(5):954-67. DOI: 10.1016/j.devcel.2012.09.021
Source: PubMed


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.

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Available from: Arnaud Echard, May 19, 2015
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    • "Bcl10 has been reported to mediate inflammatory cascades in colonic epithelial cells, mouse embryonic fibroblasts, hepatocytes, and human embryonic kidney 293T cells, as well as in cells of myeloid origin [3, 24–26]. Other recent work has identified Bcl10 as a link between fat (palmitate) intake and hepatic NF-κB activation and insulin resistance [27], and Bcl10 was reported to coordinate the NF-κB-mediated response associated with endosomal trafficking and F-actin remodeling in human macrophages [28]. Recognition of the participation of the CARMA-Bcl10-Malt1 (CBM) signalosome in vital processes in cells continues to emerge, including distinct roles of CARMA1 in immune cells and CARMA3 in epithelial/endothelial cells. "
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