title: Evolutionarily conserved coupling of adaptive and excitable networks mediates eukaryotic chemotaxis.
abstract: Numerous models explain how cells sense and migrate towards shallow chemoattractant gradients. Studies show that an excitable signal transduction network acts as a pacemaker that controls the cytoskeleton to drive motility. Here we show that this network is required to link stimuli to actin polymerization and chemotactic motility and we distinguish the various models of chemotaxis. First, signalling activity is suppressed towards the low side in a gradient or following removal of uniform chemoattractant. Second, signalling activities display a rapid shut off and a slower adaptation during which responsiveness to subsequent test stimuli decline. Simulations of various models indicate that these properties require coupled adaptive and excitable networks. Adaptation involves a G-protein-independent inhibitor, as stimulation of cells lacking G-protein function suppresses basal activities. The salient features of the coupled networks were observed for different chemoattractants in Dictyostelium and in human neutrophils, suggesting an evolutionarily conserved mechanism for eukaryotic chemotaxis.
authors.affiliation: Department of Cell Biology, Johns Hopkins School of Medicine, 725 N. Wolfe Street WBSB 116, Baltimore, Maryland 21205, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Tang
authors.affiliation: Department of Cell Biology, Johns Hopkins School of Medicine, 725 N. Wolfe Street WBSB 116, Baltimore, Maryland 21205, USA.|Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, 138 Yi Xue Yuan Road, Shanghai, 200032, China.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Electrical and Computer Engineering, Johns Hopkins University, 3400 N. Charles Street 226 Barton Hall, Baltimore, Maryland 21218, USA.
authors.forename: Changji
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Cell Biology, Johns Hopkins School of Medicine, 725 N. Wolfe Street WBSB 116, Baltimore, Maryland 21205, USA.|Department of Electrical and Computer Engineering, Johns Hopkins University, 3400 N. Charles Street 226 Barton Hall, Baltimore, Maryland 21218, USA.
authors.forename: Pablo A
authors.initials: PA
authors.lastname: Iglesias
authors.affiliation: Department of Cell Biology, Johns Hopkins School of Medicine, 725 N. Wolfe Street WBSB 116, Baltimore, Maryland 21205, USA.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Devreotes
authors.affiliation: Department of Cell Biology, Johns Hopkins School of Medicine, 725 N. Wolfe Street WBSB 116, Baltimore, Maryland 21205, USA.
authors.forename: Chuan-Hsiang
authors.initials: CH
authors.lastname: Huang
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D005075:Biological Evolution; D018914:Cells, Immobilized / Q000166:cytology / Q000187:drug effects; D002630:Chemotactic Factors / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D004023:Dictyostelium / Q000166:cytology* / Q000187:drug effects; D005057:Eukaryotic Cells / Q000166:cytology* / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002630:Chemotactic Factors; D019204:GTP-Binding Proteins