title: Control of secondary granule release in neutrophils by Ral GTPase.
abstract: Neutrophil (polymorphonuclear leukocyte; PMN) inflammatory functions, including cell adhesion, diapedesis, and phagocytosis, are dependent on the mobilization and release of various intracellular granules/vesicles. In this study, we found that treating PMN with damnacanthal, a Ras family GTPase inhibitor, resulted in a specific release of secondary granules but not primary or tertiary granules and caused dysregulation of PMN chemotactic transmigration and cell surface protein interactions. Analysis of the activities of Ras members identified Ral GTPase as a key regulator during PMN activation and degranulation. In particular, Ral was active in freshly isolated PMN, whereas chemoattractant stimulation induced a quick deactivation of Ral that correlated with PMN degranulation. Overexpression of a constitutively active Ral (Ral23V) in PMN inhibited chemoattractant-induced secondary granule release. By subcellular fractionation, we found that Ral, which was associated with the plasma membrane under the resting condition, was redistributed to secondary granules after chemoattractant stimulation. Blockage of cell endocytosis appeared to inhibit Ral translocation intracellularly. In conclusion, these results demonstrate that Ral is a critical regulator in PMN that specifically controls secondary granule release during PMN response to chemoattractant stimulation.
authors.affiliation: Department of Biology, Georgia State University, Atlanta, Georgia 30303, USA.
authors.forename: Celia X-J
authors.initials: CX
authors.lastname: Chen
authors.forename: Ileana
authors.initials: I
authors.lastname: Soto
authors.forename: Ya-Lan
authors.initials: YL
authors.lastname: Guo
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
mesh_terms: D019943:Amino Acid Substitution; D002462:Cell Membrane / Q000201:enzymology* / Q000235:genetics; D002630:Chemotactic Factors / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020125:Mutation, Missense; D018375:Neutrophil Activation / Q000187:drug effects / Q000502:physiology*; D009504:Neutrophils / Q000201:enzymology*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D022142:Secretory Vesicles / Q000378:metabolism*; D020725:ral GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002630:Chemotactic Factors; D020725:ral GTP-Binding Proteins