Differential roles of phospholipase D proteins in FcεRI-mediated signaling and mast cell function

Minghua Zhu, Jianwei Zou, Tieshi Li, Sarah A. O'Brien, Yao Zhang, Sarah Ogden, Weiguo Zhang

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4492-4502
Number of pages11
JournalJournal of Immunology
Volume195
Issue number9
DOIs
StatePublished - Nov 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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