Signalling networks in latex bead- and mycobacterial-phagosomes: Analysis of dynamics and modulation of actin-membrane assembly

点击翻译按钮获取中文摘要

In vitro assays analyse how a defined cytoplasmic membrane surface, latex bead phagosomes (LBP) from macrophages (A) assembles actin de novo and (B) binds to F-actin. In the first period we found (i) a large network of proteins and lipids that switch on actin assembly and maturation also in pathogenic mycobacterial phagosomes; (ii) a biocomputing approach identified flux modes of metabolites through the membrane, many predictions could be experimentally verified, including the synthesis of ATP; (iii) a time-step simulation to predict effects of lipid combinations on phagosomal actin under different conditions; (iv) involvement of prostaglandins and leukotrienes in actin nucleation and (v) regulation of phagosome binding to actin by arachidonate is regulated in opposite manner to actin nucleation. New work will focus on these new aspects to combine theory and experiment to provide a holistic description how these membrane signalling networks regulate actin assembly and binding: (i) kinetics and concentrations in the process of actin nucleation for key compounds; (ii) involvement of prostaglandins and other arachidonic metabolites in actin nucleation; (iii) the signalling network regulating phagosome binding to actin.