title: Identifying network motifs that buffer front-to-back signaling in polarized neutrophils.
abstract: Neutrophil polarity relies on local, mutual inhibition to segregate incompatible signaling circuits to the leading and trailing edges. Mutual inhibition alone should lead to cells having strong fronts and weak backs or vice versa. However, analysis of cell-to-cell variation in human neutrophils revealed that back polarity remains consistent despite changes in front strength. How is this buffering achieved? Pharmacological perturbations and mathematical modeling revealed a functional role for microtubules in buffering back polarity by mediating positive, long-range crosstalk from front to back; loss of microtubules inhibits buffering and results in anticorrelation between front and back signaling. Furthermore, a systematic, computational search of network topologies found that a long-range, positive front-to-back link is necessary for back buffering. Our studies suggest a design principle that can be employed by polarity networks: short-range mutual inhibition establishes distinct signaling regions, after which directed long-range activation insulates one region from variations in the other.
authors.affiliation: Green Center for Systems Biology, Department of Pharmacology, Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Wang
authors.forename: Chin-Jen
authors.initials: CJ
authors.lastname: Ku
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Zhang
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Artyukhin
authors.forename: Orion D
authors.initials: OD
authors.lastname: Weiner
authors.forename: Lani F
authors.initials: LF
authors.lastname: Wu
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Altschuler
mesh_terms: D002465:Cell Movement; D016764:Cell Polarity / Q000502:physiology; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D008962:Models, Theoretical; D009504:Neutrophils / Q000166:cytology*; D015398:Signal Transduction