Ras inhibitor CAPRI enables neutrophil-like cells to chemotax through a higher-concentration range of gradients
Xuehua Xu, Xi Wen, Amer Moosa, Smit Bhimani, Tian Jin
Abstract
Significance Neutrophils provide first-line host defense by migrating through chemoattractant gradients to the sites of inflammation. The inappropriate recruitment and misregulated activation of neutrophils contribute to tissue damage and cause autoimmune and inflammatory disease. One fascinating feature of chemotactic neutrophils is their ability to migrate through an enormous concentration range of chemoattractant gradients (10 −9 to ∼10 −5 M) through “adaptation,” in which cells no longer respond to the present stimuli but remain sensitive to stronger stimuli. The inhibitory mechanism largely remains elusive, although many molecules of the excitatory signaling pathway have been identified. Our study reveals that the inhibitory component, CAPRI, is essential for both the sensitivity and the GPCR-mediated adaptation of human neutrophils.