title: Store-operated Ca2+ entry (SOCE) plays a role in the polarization of neutrophil-like HL-60 cells by regulating the activation of Akt, Src, and Rho family GTPases.
abstract: Neutrophil polarization is a basic activity involved in the innate immune response, and it may be initiated by extracellular Ca(2+) entry, a process primarily mediated through store-operated Ca(2+) entry (SOCE). Yet, the mechanisms by which SOCE participates in cell polarization remain unclear. We hypothesized that Akt- and Src-dependent pathways, traditionally linked to neutrophil polarization, may interact with SOCE in this event. In this study, SKF96365 and 2-APB, inhibitors of SOCE as proved by their inhibition on Mn(2+) influx, were observed to inhibit the formyl-methionyl-leucyl-phenylalanine (fMLP)-induced influx of Ca(2+), the activation of Akt, Src, Rac1, Rac2, and Cdc42, and the polarization of differentiated HL-60 (dHL-60) cells. Downregulation of stromal interaction molecule 1 (STIM1), a Ca(2+) sensor identified to induce SOCE, by siRNA led to decreases in the following indexes: Ca(2+) entry, activation of Akt, Src, Rac2 (rather than Rac1) and Cdc42, and fMLP-induced polarization. This study suggests that SOCE might be the predominant form of Ca(2+) entry involved in the regulation of cell polarization, and it may act through the Akt/Src/Rac pathways, as modeled in dHL-60 cells. It also suggests that STIM1 is a key modulator of cell polarization, potentially serving as a target for the designation of anti-immune deficiency therapies.
authors: Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
authors: Wenying
authors: W
authors: Zou
authors: Xiaojing
authors: X
authors: Meng
authors: Chunqing
authors: C
authors: Cai
authors: Mengchen
authors: M
authors: Zou
authors: Shihao
authors: S
authors: Tang
authors: Xinwei
authors: X
authors: Chu
authors: Xubu
authors: X
authors: Wang
authors: Fei
authors: F
authors: Zou
mesh_terms: D001896:Boron Compounds / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling; D016764:Cell Polarity; D004789:Enzyme Activation; D055785:Gene Knockdown Techniques; D018922:HL-60 Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008345:Manganese / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D000071737:Stromal Interaction Molecule 1; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D001896:Boron Compounds; D002121:Calcium Channel Blockers; D007093:Imidazoles; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D008345:Manganese; D009240:N-Formylmethionine Leucyl-Phenylalanine; C109986:2-aminoethoxydiphenyl borate; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D020741:rho GTP-Binding Proteins; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole