Abstract:
:Polarity in mammalian cells emerges from the assembly of signaling molecules into extensive biochemical interaction networks. Despite their complexity, bacterial pathogens have evolved parsimonious mechanisms to hijack these systems. Here, we develop a tractable experimental and theoretical model to uncover fundamental operating principles, in both mammalian cell polarity and bacterial pathogenesis. Using synthetic derivatives of the enteropathogenic Escherichia coli guanine-nucleotide exchange factor (GEF) Map, we discover that Cdc42 GTPase signal transduction is controlled by the interaction between Map and F-actin. Mathematical modeling reveals how actin dynamics coupled to a Map-dependent positive feedback loop spontaneously polarizes Cdc42 on the plasma membrane. By rewiring the pathogenic signaling circuit to operate through β-integrin stimulation, we further show how Cdc42 is polarized in response to an extracellular spatial cue. Thus, a molecular pathway of polarity is proposed, centered on the interaction between GEFs and F-actin, which is likely to function in diverse biological systems.
journal_name
Celljournal_title
Cellauthors
Orchard RC,Kittisopikul M,Altschuler SJ,Wu LF,Süel GM,Alto NMdoi
10.1016/j.cell.2011.11.063subject
Has Abstractpub_date
2012-02-17 00:00:00pages
803-15issue
4eissn
0092-8674issn
1097-4172pii
S0092-8674(12)00024-4journal_volume
148pub_type
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