title: Glia maturation factor-γ mediates neutrophil chemotaxis.
abstract: Chemotaxis is fundamental to the directional migration of neutrophils toward endogenous and exogenous chemoattractants. Recent studies have demonstrated that ADF/cofilin superfamily members play important roles in reorganizing the actin cytoskeleton by disassembling actin filaments. GMFG, a novel ADF/cofilin superfamily protein that is expressed in inflammatory cells, has been implicated in regulating actin reorganization in microendothelial cells, but its function in neutrophils remains unclear. Here, we show that GMFG is an important regulator for cell migration and polarity in neutrophils. Knockdown of endogenous GMFG impaired fMLF- and IL-8 (CXCL8)-induced chemotaxis in dHL-60 cells. GMFG knockdown attenuated the formation of lamellipodia at the leading edge of cells exposed to fMLF or CXCL8, as well as the phosphorylation of p38 and PAK1/2 in response to fMLF or CXCL8. Live cell imaging revealed that GMFG was recruited to the leading edge of cells in response to fMLF, as well as CXCL8. Overexpression of GMFG enhanced phosphorylation of p38 but not of PAK1/2 in dHL-60 cells. In addition, we found that GMFG is associated with WAVE2. Taken together, our findings suggest that GMFG is a novel factor in regulating neutrophil chemotaxis by modulating actin cytoskeleton reorganization.
authors.affiliation: Molecular and Clinical Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-2560, USA.
authors.forename: Wulin
authors.initials: W
authors.lastname: Aerbajinai
authors.forename: Lunhua
authors.initials: L
authors.lastname: Liu
authors.forename: Kyung
authors.initials: K
authors.lastname: Chin
authors.forename: Jianqiong
authors.initials: J
authors.lastname: Zhu
authors.forename: Carole A
authors.initials: CA
authors.lastname: Parent
authors.forename: Griffin P
authors.initials: GP
authors.lastname: Rodgers
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D016764:Cell Polarity; D049109:Cell Proliferation; D002478:Cells, Cultured; D002633:Chemotaxis; D003599:Cytoskeleton / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020904:Glia Maturation Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D016209:Interleukin-8 / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D011554:Pseudopodia / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D020904:Glia Maturation Factor; D016209:Interleukin-8; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C117487:glia maturation factor gamma; C515903:PAK1 protein, human; D054462:p21-Activated Kinases; D048051:p38 Mitogen-Activated Protein Kinases