1. SHEP1 partners with CasL to promote marginal zone B-cell maturation.
- Author
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Browne CD, Hoefer MM, Chintalapati SK, Cato MH, Wallez Y, Ostertag DV, Pasquale EB, and Rickert RC
- Subjects
- Adaptor Proteins, Signal Transducing genetics, Animals, B-Lymphocytes cytology, Lysophospholipids genetics, Lysophospholipids metabolism, Mice, Mice, Knockout, Phosphorylation physiology, Receptors, Antigen, B-Cell genetics, Receptors, Antigen, B-Cell metabolism, Receptors, Lysosphingolipid genetics, Receptors, Lysosphingolipid metabolism, Sphingosine analogs & derivatives, Sphingosine genetics, Sphingosine metabolism, Spleen cytology, Adaptor Proteins, Signal Transducing metabolism, B-Lymphocytes metabolism, Cell Movement physiology, Signal Transduction physiology, Spleen metabolism
- Abstract
The marginal zone is a cellular niche bordering the marginal sinus of the spleen that contains specialized B-cell and macrophage subsets poised to capture bloodborne antigens. Marginal zone B cells are retained in this niche by integrin-mediated signaling induced by G protein-coupled receptors (GPCRs) and, likely, the B-cell receptor (BCR). Sphingosine-1-phosphate (S1P) signaling via the S1P family of GPCRs is known to be essential for B-cell localization in the marginal zone, but little is known about the downstream signaling events involved. Here, we demonstrate that the adaptor protein SHEP1 is required for marginal zone B-cell maturation. SHEP1 functions in concert with the scaffolding protein CasL, because we show that SHEP1 and CasL are constitutively associated in B cells. SHEP1 association is required for the BCR or S1P receptor(s) to induce the conversion of CasL into its serine/threonine hyperphosphorylated form, which is important for lymphocyte adhesion and motility. Thus, SHEP1 orchestrates marginal zone B-cell movement and retention as a key downstream effector of the BCR and S1P receptors.
- Published
- 2010
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