flotillins interact with psgl-1 in neutrophils and, upon stimulation, rapidly organize into membrane domains subsequently accumulating in the uropodflotillins psgl-1中性粒细胞和交互,在刺激,随后迅速组织成膜领域积累的腹足.pdfVIP

Flotillins Interact with PSGL-1 in Neutrophils and, upon Stimulation, Rapidly Organize into Membrane Domains Subsequently Accumulating in the Uropod ´ ´ 1 1¤ 2 1 Jeremie Rossy , Dominique Schlicht , Britta Engelhardt , Verena Niggli * 1 Department of Pathology, University of Bern, Bern, Switzerland, 2 Theodor Kocher Institute, University of Bern, Bern, Switzerland Abstract Background: Neutrophils polarize and migrate in response to chemokines. Different types of membrane microdomains (rafts) have been postulated to be present in rear and front of polarized leukocytes and disruption of rafts by cholesterol sequestration prevents leukocyte polarization. Reggie/flotillin-1 and -2 are two highly homologous proteins that are ubiquitously enriched in detergent resistant membranes and are thought to shape membrane microdomains by forming homo- and hetero-oligomers. It was the goal of this study to investigate dynamic membrane microdomain reorganization during neutrophil activation. Methodology/Principal Findings: We show now, using immunofluorescence staining and co-immunoprecipitation, that endogenous flotillin-1 and -2 colocalize and associate in resting spherical and polarized primary neutrophils. Flotillins redistribute very early after chemoattractant stimulation, and form distinct caps in more than 90% of the neutrophils. At later time points flotillins accumulate in the uropod of polarized cells. Chemotactic peptide-induced redistribution and capping of flotillins requires integrity and dynamics of the actin cytoskeleton, but does not involve Rho-kinase dependent signaling related to formation of the uropod. Both flotillin isoforms are involved in the formation of this