title: Differential Roles of Phospholipase D Proteins in FcεRI-Mediated Signaling and Mast Cell Function.
abstract: Phospholipase D (PLD) proteins are enzymes that catalyze the hydrolysis of phosphatidylcholine to generate an important signaling lipid, phosphatidic acid. Phosphatidic acid is a putative second messenger implicated in the regulation of vesicular trafficking and cytoskeletal reorganization. Previous studies using inhibitors and overexpression of PLD proteins indicate that PLD1 and PLD2 play positive roles in FcεRI-mediated signaling and mast cell function. We used mice deficient in PLD1, PLD2, or both to study the function of these enzymes in mast cells. In contrast to published studies, we found that PLD1 deficiency impaired FcεRI-mediated mast cell degranulation; however, PLD2 deficiency enhanced it. Biochemical analysis showed that PLD deficiency affected activation of the PI3K pathway and RhoA. Furthermore, our data indicated that, although PLD1 deficiency impaired F-actin disassembly, PLD2 deficiency enhanced microtubule formation. Together, our results suggested that PLD1 and PLD2, two proteins that catalyze the same enzymatic reaction, regulate different steps in mast cell degranulation.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Minghua
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Tieshi
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: O'Brien
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ogden
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710 zhang033@mc.duke.edu.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000199:Actins / Q000276:immunology / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D015550:Cell Degranulation / Q000276:immunology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology / Q000378:metabolism; D010739:Phospholipase D / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D017455:Receptors, IgE / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D020742:rhoA GTP-Binding Protein / Q000276:immunology / Q000378:metabolism
chemical_list: D000199:Actins; D017455:Receptors, IgE; D019869:Phosphatidylinositol 3-Kinases; C105606:phospholipase D2; D010739:Phospholipase D; C106801:phospholipase D1; D020742:rhoA GTP-Binding Protein