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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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Wang Y,Ku CJ,Zhang ER,Artyukhin AB,Weiner OD,Wu LF,Altschuler SJ

doi

10.1016/j.celrep.2013.04.009

subject

Has Abstract

pub_date

2013-05-30 00:00:00

pages

1607-16

issue

5

issn

2211-1247

pii

S2211-1247(13)00176-9

journal_volume

3

pub_type

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