The C Terminus of SipC Binds and Bundles F-actin to Promote Salmonella Invasion

Myeni, Sebenzile K.; Zhou, Daoguo

doi:10.1074/jbc.m109.094045

Cited by 64 publications

(66 citation statements)

References 32 publications

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“…Recently, mutant bacteria lacking the C-terminal region of SipC responsible for F-actin binding and bundling were found to be less invasive than wild-type Salmonella, suggesting that the bundling activity of SipC plays a role in pathogen entry into HeLa cells (23). Whether Tarp's ability to bundle actin filaments also contributes to pathogen entry is unknown but worthy of investigation, as new molecular tools continue to be developed to examine the genetic requirements of C. trachomatis pathogenicity (24,25).…”

Section: Discussionmentioning

confidence: 99%

Chlamydia trachomatis Tarp Harbors Distinct G and F Actin Binding Domains That Bundle Actin Filaments

Jiwani

Alvarado

Ohr

et al. 2012

Journal of Bacteriology

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All species of Chlamydia undergo a unique developmental cycle that transitions between extracellular and intracellular environments and requires the capacity to invade new cells for dissemination. A chlamydial protein called Tarp has been shown to nucleate actin in vitro and is implicated in bacterial entry into human cells. Colocalization studies of ectopically expressed enhanced green fluorescent protein (EGFP)-Tarp indicate that actin filament recruitment is restricted to the C-terminal half of the effector protein. Actin filaments are presumably associated with Tarp via an actin binding alpha helix that is also required for actin nucleation in vitro, but this has not been investigated. Tarp orthologs from C. pneumoniae, C. muridarum, and C. caviae harbor between 1 and 4 actin binding domains located in the C-terminal half of the protein, but C. trachomatis serovar L2 has only one characterized domain. In this work, we examined the effects of domain-specific mutations on actin filament colocalization with EGFP-Tarp. We now demonstrate that actin filament colocalization with Tarp is dependent on two novel F-actin binding domains that endow the Tarp effector with actin-bundling activity. Furthermore, Tarp-mediated actin bundling did not require actin nucleation, as the ability to bundle actin filaments was observed in mutant Tarp proteins deficient in actin nucleation. These data shed molecular insight on the complex cytoskeletal rearrangements required for C. trachomatis entry into host cells.

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Section: Discussionmentioning

confidence: 99%

Chlamydia trachomatis Tarp Harbors Distinct G and F Actin Binding Domains That Bundle Actin Filaments

Jiwani

Alvarado

Ohr

et al. 2012

Journal of Bacteriology

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“…Residues 201-220 of SipC are necessary for its actin nucleation activity, whereas the C-terminal 88 amino acids are important for its translocase function [23]. Initial studies ascribed the F-actin bundling activity of SipC to its N-terminal domain [244], but a more recent report suggests that this activity is directed by residues 221-260 and 381-409 in the C-terminal region [24]. The C-terminal region is also involved in the interaction with cytokeratin 8 [245,246].…”

Section: Sipb Sipc and Sipdmentioning

confidence: 99%

“…SipA modulates the actin-bundling activity of T-plastin [21] and inhibits the filament-depolymerizing factor ADF/cofilin and the filament capping and severin protein gelsolin [22]. SipC possesses distinct domains that are able to nucleate actin (central amino acid region) and to promote actin bundling (Cterminal region) [23,24]. SopE, SopE2, and SopB do not directly interact with actin but mediate the activation of small GTPases of the Rho family that are required for the formation of highly branched actin networks.…”

Section: Actin Cytoskeleton and Invasionmentioning

confidence: 99%

Impact ofSalmonella entericaType III Secretion System Effectors on the Eukaryotic Host Cell

Ramos‐Morales

2012

ISRN Cell Biology

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Type III secretion systems are molecular machines used by many Gram-negative bacterial pathogens to inject proteins, known as effectors, directly into eukaryotic host cells. These proteins manipulate host signal transduction pathways and cellular processes to the pathogen's advantage. Salmonella enterica possesses two virulence-related type III secretion systems that deliver more than forty effectors. This paper reviews our current knowledge about the functions, biochemical activities, host targets, and impact on host cells of these effectors. First, the concerted action of effectors at the cellular level in relevant aspects of the interaction between Salmonella and its hosts is analyzed. Then, particular issues that will drive research in the field in the near future are discussed. Finally, detailed information about each individual effector is provided.

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“…The C-terminal region of SipC (aminoacids A321-A409) encodes the effector translocation activity (Chang et al, 2005) and its central region (amino-acids N201-S220) binds to actin and induces a rapid nucleation and elongation of actin filaments. More precisely the regions containing the amino acids from H221-M260 and L381-A409 bind to and bundle actin filaments in vitro (Myeni & Zhou, 2010). The bundling activity of SipC is essential for internalization as a sipC mutant lacking bundling activity is impaired in cell invasion.…”

Section: Actin Manipulationmentioning

confidence: 99%