Swiprosin-1/EFhd2 Controls B Cell Receptor Signaling through the Assembly of the B Cell Receptor, Syk, and Phospholipase C gamma 2 in Membrane Rafts

Kroczek C, Lang C, Brachs S, Grohmann M, Duetting S, Schweizer A, Nitschke L, Feller SM, Jäck HM, Mielenz D (2010)

Publication Status: Published

Publication Type: Journal article

Publication year: 2010

Journal

Publisher: AMER ASSOC IMMUNOLOGISTS

Book Volume: 184

Pages Range: 3665-3676

Journal Issue: 7

DOI: 10.4049/jimmunol.0903642

Abstract

Compartmentalization of the BCR in membrane rafts is important for its signaling capacity. Swiprosin-1/EFhd2 (Swip-1) is an EF-hand and coiled-coil-containing adaptor protein with predicted Src homology 3 (SH3) binding sites that we identified in membrane rafts. We showed previously that Swip-1 amplifies BCR-induced apoptosis; however, the mechanism of this amplification was unknown. To address this question, we overexpressed Swip-1 and found that Swip-1 amplified the BCR-induced calcium flux in WEH1231, B62.1, and Bal17 cells. Conversely, the BCR-elicited calcium flux was strongly attenuated in Swip-1-silenced WEH1231 cells, and this was due to a decreased calcium mobilization from intracellular stores. Complementation of Swip-1 expression in Swip-1-silenced WEH1231 cells restored the BCR-induced calcium flux and enhanced spleen tyrosine kinase (Syk) tyrosine phosphorylation and activity as well as SLP65/BLNK/BASH and phospholipase C gamma 2 (PLC gamma 2) tyrosine phosphorylation. Furthermore, Swip-1 induced the constitutive association of the BCR itself, Syk, and PLC gamma 2 with membrane rafts. Concomitantly, Swip-1 stabilized the association of BCR with tyrosine-phosphorylated proteins, specifically Syk and PLC gamma 2, and enhanced the constitutive interaction of Syk and PLC gamma 2 with Lyn. Interestingly, Swip-1 bound to the rSH3 domains of the Src kinases Lyn and Fgr, as well as to that of PLC gamma. Deletion of the predicted SH3-binding region in Swip-1 diminished its association and that of Syk and PLC gamma 2 with membrane rafts, reduced its interaction with the SH3 domain of PLC gamma, and diminished the BCR-induced calcium flux. Hence, Swip-1 provides a membrane scaffold that is required for the Syk-, SLP-65-, and PLC gamma 2-dependent BCR-induced calcium flux. The Journal of Immunology, 2010, 184: 3665-3676.

Authors with CRIS profile

Involved external institutions

University of Oxford United Kingdom (GB)

How to cite

APA:

Kroczek, C., Lang, C., Brachs, S., Grohmann, M., Duetting, S., Schweizer, A.,... Mielenz, D. (2010). Swiprosin-1/EFhd2 Controls B Cell Receptor Signaling through the Assembly of the B Cell Receptor, Syk, and Phospholipase C gamma 2 in Membrane Rafts. Journal of Immunology, 184(7), 3665-3676. https://dx.doi.org/10.4049/jimmunol.0903642

MLA:

Kroczek, Carmen, et al. "Swiprosin-1/EFhd2 Controls B Cell Receptor Signaling through the Assembly of the B Cell Receptor, Syk, and Phospholipase C gamma 2 in Membrane Rafts." Journal of Immunology 184.7 (2010): 3665-3676.

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