WIP regulates signaling via the high affinity receptor for immunoglobulin E in mast cells.
Wiskott-Aldrich syndrome protein-interacting protein (WIP) stabilizes actin filaments and is important for immunoreceptor-mediated signal transduction leading to actin cytoskeleton rearrangement in T and B cells. Here we report a role for WIP in signaling pathways downstream of the high affinity receptor for immunoglobulin (Ig)E (FcepsilonRI) in mast cells. WIP-deficient bone marrow-derived mast cells (BMMCs) were impaired in their capacity to degranulate and secrete interleukin 6 after FcepsilonRI ligation. Calcium mobilization, phosphorylation of Syk, phospholipase C-g2, and c-Jun NH2-terminal kinase were markedly decreased in WIP-deficient BMMCs. WIP was found to associate with Syk after FcepsilonRI ligation and to inhibit Syk degradation as evidenced by markedly diminished Syk levels in WIP-deficient BMMCs. WIP-deficient BMMCs exhibited no apparent defect in their subcortical actin network and were normal in their ability to form protrusions when exposed to an IgE-coated surface. However, the kinetics of actin changes and the cell shape changes that follow FcepsilonRI signaling were altered in WIP-deficient BMMCs. These results suggest that WIP regulates FcepsilonRI-mediated mast cell activation by regulating Syk levels and actin cytoskeleton rearrangement.
Kettner
Alexander
A
Division of Immunology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Kumar
Lalit
L
Antón
Inés M
IM
Sasahara
Yoji
Y
de la Fuente
Miguel
M
Pivniouk
Vadim I
VI
Falet
Hervé
H
Hartwig
John H
JH
Geha
Raif S
RS
D000199:Actins / Q000502:physiology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D003598:Cytoskeletal Proteins; D017353:Gene Deletion; D006636:Histamine Release; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D017455:Receptors, IgE / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014923:Wiskott-Aldrich Syndrome / Q000276:immunology*
D000199:Actins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017455:Receptors, IgE; C109903:WIPF1 protein, human; C491671:Waspip protein, mouse