Abstract
Numerous models have been proposed to explain the remarkable ability of chemotactic cells to sense and migrate toward extremely shallow chemoattractant gradients independently of the ambient concentration. We carried out experiments to distinguish the various models of gradient sensing in migrating cells. First, signaling activity was strongly suppressed toward the low side of cells in a gradient or following sudden removal of uniform chemoattractant. Second, signaling activities displayed a rapid shut off and, with stimulation of increasing duration, a slower adaptation during which responsiveness to subsequent test stimuli declined. Simulations of existing classes of models indicated that these observations can only be explained by the coupling between an adaptive module and an excitable network. Moreover, stimulation of cells lacking G-protein function suppresses downstream activities, while constitutive G-protein activation induced persistent responses. This indicates that chemoattractant sensing is mediated by a G-protein-dependent excitor and a G-protein-independent inhibitor forming an incoherent feedforward loop. The salient features of the coupling between adaptive and excitable networks were observed for the chemoattractants cAMP and folic acid in Dictyostelium as well as fMLP in human neutrophils, suggesting an evolutionarily conserved mechanism for eukaryotic chemotaxis.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.