The type III effector EspF coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathways

Neal M. Alto, Andrew W. Weflen, Matthew J. Rardin, Defne Yarar, Cheri S. Lazar, Raffi Tonikian, Antonius Koller, Susan S. Taylor, Charles Boone, Sachdev S. Sidhu, Sandra L. Schmid, Gail A. Hecht, Jack E. Dixon

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Bacterial toxins and effector proteins hijack eukaryotic enzymes that are spatially localized and display rapid signaling kinetics. However, the molecular mechanisms by which virulence factors engage highly dynamic substrates in the host cell environment are poorly understood. Here, we demonstrate that the enteropathogenic Escherichia coli (EPEC) type III effector protein EspF nucleates a multiprotein signaling complex composed of eukaryotic sorting nexin 9 (SNX9) and neuronal Wiskott-Aldrich syndrome protein (N-WASP). We demonstrate that a specific and high affinity association between EspF and SNX9 induces membrane remodeling in host cells. These membrane-remodeling events are directly coupled to N-WASP/Arp2/3-mediated actin nucleation. In addition to providing a biochemical mechanism of EspF function, we find that EspF dynamically localizes to membranetraffi cking organelles in a spatiotemporal pattern that correlates with SNX9 and N-WASP activity in living cells. Thus, our findings suggest that the EspF-dependent assembly of SNX9 and N-WASP represents a novel form of signaling mimicry used to promote EPEC pathogenesis and gastrointestinal disease.

Original languageEnglish (US)
Pages (from-to)1265-1278
Number of pages14
JournalJournal of Cell Biology
Volume178
Issue number7
DOIs
StatePublished - Sep 24 2007

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Neuronal Wiskott-Aldrich Syndrome Protein
Sorting Nexins
Enteropathogenic Escherichia coli
Membranes
Bacterial Toxins
Multiprotein Complexes
Gastrointestinal Diseases
Virulence Factors
Organelles
Actins
Proteins
Enzymes

ASJC Scopus subject areas

  • Cell Biology

Cite this

The type III effector EspF coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathways. / Alto, Neal M.; Weflen, Andrew W.; Rardin, Matthew J.; Yarar, Defne; Lazar, Cheri S.; Tonikian, Raffi; Koller, Antonius; Taylor, Susan S.; Boone, Charles; Sidhu, Sachdev S.; Schmid, Sandra L.; Hecht, Gail A.; Dixon, Jack E.

In: Journal of Cell Biology, Vol. 178, No. 7, 24.09.2007, p. 1265-1278.

Research output: Contribution to journalArticle

Alto, NM, Weflen, AW, Rardin, MJ, Yarar, D, Lazar, CS, Tonikian, R, Koller, A, Taylor, SS, Boone, C, Sidhu, SS, Schmid, SL, Hecht, GA & Dixon, JE 2007, 'The type III effector EspF coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathways', Journal of Cell Biology, vol. 178, no. 7, pp. 1265-1278. https://doi.org/10.1083/jcb.200705021
Alto, Neal M. ; Weflen, Andrew W. ; Rardin, Matthew J. ; Yarar, Defne ; Lazar, Cheri S. ; Tonikian, Raffi ; Koller, Antonius ; Taylor, Susan S. ; Boone, Charles ; Sidhu, Sachdev S. ; Schmid, Sandra L. ; Hecht, Gail A. ; Dixon, Jack E. / The type III effector EspF coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathways. In: Journal of Cell Biology. 2007 ; Vol. 178, No. 7. pp. 1265-1278.
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