title: Cutting Edge: Drebrin-Regulated Actin Dynamics Regulate IgE-Dependent Mast Cell Activation and Allergic Responses.
abstract: Mast cells play critical roles in allergic responses. Calcium signaling controls the function of these cells, and a role for actin in regulating calcium influx into cells has been suggested. We have previously identified the actin reorganizing protein Drebrin as a target of the immunosuppressant 3,5-bistrifluoromethyl pyrazole, which inhibits calcium influx into cells. In this study, we show that Drebrin(-/-) mice exhibit reduced IgE-mediated histamine release and passive systemic anaphylaxis, and Drebrin(-/-) mast cells also exhibit defects in FcεRI-mediated degranulation. Drebrin(-/-) mast cells exhibit defects in actin cytoskeleton organization and calcium responses downstream of the FcεRI, and agents that relieve actin reorganization rescue mast cell FcεRI-induced degranulation. Our results indicate that Drebrin regulates the actin cytoskeleton and calcium responses in mast cells, thus regulating mast cell function in vivo.
authors.affiliation: Center for Molecular Immunology and Infectious Disease and Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16801; Immunology and Infectious Diseases Graduate Program, Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16801; Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853; and.
authors.forename: Mankit
authors.initials: M
authors.lastname: Law
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853; and.
authors.forename: YongChan
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Center for Molecular Immunology and Infectious Disease and Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16801;
authors.forename: J Luis
authors.initials: JL
authors.lastname: Morales
authors.affiliation: Microscopy and Cytometry Facility, Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16801.
authors.forename: Gang
authors.initials: G
authors.lastname: Ning
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853; and.
authors.forename: Weishan
authors.identifier: http://orcid.org/0000-0002-1330-1131
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853; and.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pabon
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853; and.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Kannan
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853; and.
authors.forename: Ah-Reum
authors.initials: AR
authors.lastname: Jeong
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853; and.
authors.forename: Amie
authors.initials: A
authors.lastname: Wood
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853; and.
authors.forename: Chavez
authors.initials: C
authors.lastname: Carter
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853; and.
authors.forename: Sonia
authors.initials: S
authors.lastname: Mohinta
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853; and.
authors.forename: Jihong
authors.initials: J
authors.lastname: Song
authors.affiliation: Center for Molecular Immunology and Infectious Disease and Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16801; Immunology and Infectious Diseases Graduate Program, Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16801; Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853; and averyaugust@cornell.edu.
authors.forename: Avery
authors.identifier: http://orcid.org/0000-0003-4968-3415
authors.initials: A
authors.lastname: August
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D000199:Actins / Q000235:genetics / Q000276:immunology*; D000707:Anaphylaxis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D015550:Cell Degranulation / Q000276:immunology; D005786:Gene Expression Regulation; D007073:Immunoglobulin E / Q000008:administration & dosage / Q000737:chemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides / Q000235:genetics / Q000276:immunology*; D011720:Pyrazoles / Q000494:pharmacology; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D012709:Serum Albumin / Q000737:chemistry / Q000276:immunology
chemical_list: D000199:Actins; C485701:Fcgr1 protein, mouse; D007166:Immunosuppressive Agents; D009479:Neuropeptides; D011720:Pyrazoles; D017452:Receptors, IgG; D012709:Serum Albumin; C053386:drebrins; D007073:Immunoglobulin E; D002118:Calcium