Title

Critical Role for the Host GTPase-Activating Protein ARAP2 in InlB-Mediated Entry of Listeria monocytogenes

Authors

Authors

B. Gavicherla; L. Ritchey; A. Gianfelice; A. A. Kolokoltsov; R. A. Davey;K. Ireton

Comments

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Abbreviated Journal Title

Infect. Immun.

Keywords

ACTIN CYTOSKELETON; PHOSPHOINOSITIDE 3-KINASE; BACTERIAL INVASION; TYROSINE KINASE; ARF6; CLATHRIN; CELLS; INTERNALIZATION; RAC1; PHAGOCYTOSIS; Immunology; Infectious Diseases

Abstract

The bacterial pathogen Listeria monocytogenes causes food-borne illnesses culminating in gastroenteritis, meningitis, or abortion. Listeria induces its internalization into some mammalian cells through binding of the bacterial surface protein InlB to the host receptor tyrosine kinase Met. Interaction of InlB with the Met receptor elicits host downstream signaling pathways that promote F-actin cytoskeletal changes responsible for pathogen engulfment. Here we show that the mammalian signaling protein ARAP2 plays a critical role in cytoskeletal remodeling and internalization of Listeria. Depletion of ARAP2 through RNA interference (RNAi) caused a marked inhibition of InlB-mediated F-actin rearrangements and bacterial entry. ARAP2 contains multiple functional domains, including a GTPase-activating protein (GAP) domain that antagonizes the GTPase Arf6 and a domain capable of binding the GTPase RhoA. Genetic data indicated roles for both the Arf GAP and RhoA binding domains in Listeria entry. Experiments involving Arf6 RNAi or a constitutively activated allele of Arf6 demonstrated that one of the ways in which ARAP2 promotes bacterial uptake is by restraining the activity of Arf6. Conversely, Rho activity was dispensable for Listeria internalization, suggesting that the RhoA binding domain in ARAP2 acts by engaging a host ligand other than Rho proteins. Collectively, our findings indicate that ARAP2 promotes InlB-mediated entry of Listeria, in part, by antagonizing the host GTPase Arf6.

Journal Title

Infection and Immunity

Volume

78

Issue/Number

11

Publication Date

1-1-2010

Document Type

Article

Language

English

First Page

4532

Last Page

4541

WOS Identifier

WOS:000283052100009

ISSN

0019-9567

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