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SHR Neuro Cancer Cardio Lipid Metab Microb
Keppler, SJ; Burbage, M; Gasparrini, F; Hartjes, L; Aggarwal, S; Massaad, MJ; Geha, RS; Bruckbauer, A; Batista, FD.
The Lack of WIP Binding to Actin Results in Impaired B Cell Migration and Altered Humoral Immune Responses.
Cell Rep. 2018; 24(3): 619-629.
Doi: 10.1016/j.celrep.2018.06.051
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- Leading authors Med Uni Graz
- Keppler Selina Jessica
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- Abstract:
- Wiskott-Aldrich syndrome protein (WASp) is a main cytoskeletal regulator in B cells. WASp-interacting protein (WIP) binds to and stabilizes WASp but also interacts with actin. Using mice with a mutated actin binding domain of WIP (WIPΔABD), we here investigated the role of WIP binding to actin during B cell activation. We found an altered differentiation of WIPΔABD B cells and diminished antibody affinity maturation after immunization. Mechanistically, WIPΔABD B cells showed impaired B cell receptor (BCR)-induced PI3K signaling and actin reorganization, likely caused by diminished CD81 expression and altered CD19 dynamics on the B cell surface. WIPΔABD B cells displayed reduced in vivo motility, concomitantly with impaired chemotaxis and defective F-actin polarization, HS1 phosphorylation, and polarization of HS1 to F-actin-rich structures after CXCL12 stimulation in vitro. We thus concluded that WIP binding to actin, independent of its binding to WASp, is critical for actin cytoskeleton plasticity in B cells.
- Find related publications in this database (using NLM MeSH Indexing)
- Actins - metabolism
- Animals - administration & dosage
- Antibody Affinity - administration & dosage
- Antigens, CD - metabolism
- B-Lymphocytes - cytology, metabolism
- Carrier Proteins - metabolism
- Cell Membrane - metabolism
- Cell Movement - administration & dosage
- Cell Polarity - administration & dosage
- Chemotaxis - administration & dosage
- Cytoskeletal Proteins - administration & dosage
- Diffusion - administration & dosage
- Germinal Center - metabolism
- Granulocyte Colony-Stimulating Factor - metabolism
- Immunity, Humoral - administration & dosage
- Mice - administration & dosage
- Phosphatidylinositol 3-Kinases - metabolism
- Protein Binding - administration & dosage
- Receptors, Antigen, B-Cell - metabolism
- Signal Transduction - administration & dosage