期刊
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
卷 368, 期 1629, 页码 -出版社
ROYAL SOC
DOI: 10.1098/rstb.2013.0008
关键词
actin; receptor; neutrophil; adaptation; cell polarity; chemotaxis
类别
资金
- Achievement Rewards for College Scientists (ARCS) Scholarship
- National Institutes of Health [5T32EB009383-03, R01 GM084040]
- California Institute for Regenerative Medicine fellowship [TG2-01153]
- National Institutes of Health Nanomedicine Development Center [PN2EY016546]
Neutrophils are cells of the innate immune system that hunt and kill pathogens using directed migration. This process, known as chemotaxis, requires the regulation of actin polymerization downstream of chemoattractant receptors. Reciprocal interactions between actin and intracellular signals are thought to underlie many of the sophisticated signal processing capabilities of the chemotactic cascade including adaptation, amplification and long-range inhibition. However, with existing tools, it has been difficult to discern actin's role in these processes. Most studies investigating the role of the actin cytoskeleton have primarily relied on actin-depolymerizing agents, which not only block new actin polymerization but also destroy the existing cytoskeleton. We recently developed a combination of pharmacological inhibitors that stabilizes the existing actin cytoskeleton by inhibiting actin polymerization, depolymerization and myosin-based rearrangements; we refer to these processes collectively as actin dynamics. Here, we investigated how actin dynamics influence multiple signalling responses (PI3K lipid products, calcium and Pak phosphorylation) following acute agonist addition or during desensitization. We find that stabilized actin polymer extends the period of receptor desensitization following agonist binding and that actin dynamics rapidly reset receptors from this desensitized state. Spatial differences in actin dynamics may underlie front/back differences in agonist sensitivity in neutrophils.
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