scholarly journals The Chlamydia trachomatis type III effector TarP coordinates a functional collaboration between the actin nucleators Formin 1 and Arp2/3 during invasion

2021 ◽  
Author(s):  
Matthew D. Romero ◽  
Carabeo A. Carabeo
Keyword(s):  
Chlamydia Trachomatis ◽  
Population Level ◽  
Actin Dynamics ◽  
Actin Remodeling ◽  
Type Iii Effector ◽  
Type Iii ◽  
Obligate Intracellular Pathogen ◽  
Pathogen Entry ◽  
Kinetics Of ◽  
Slow Turnover

The obligate intracellular pathogen Chlamydia trachomatis manipulates the host actin cytoskeleton to assemble actin-rich structures that drive pathogen entry. This actin remodeling event exhibits relatively rapid dynamics that, through quantitative live-cell imaging, was revealed to consist of three phases – a fast recruitment phase which abruptly transitions to a fast turnover phase before resolving into a slow turnover of actin that indicates the end of actin remodeling. Here, we investigate Chlamydia invasion in the context of actin dynamics. Efficient invasion is associated with robust actin remodeling kinetics that results from a collaborative functional interaction between two different classes of actin nucleators – formins, including formin 1 and the diaphanous-related formins mDia1 and mDia2, and the Arp2/3 complex. Recruitment of these nucleators requires the presence of the chlamydial type III effector TarP, which enables the respective nucleating activities of formin and Arp2/3 to collaboratively generate a robust actin network. A collaborative model is supported by the observation that co-inhibition of Fmm1 and Arp2/3 further reduced both actin dynamics and invasion efficiency than either treatment alone. Furthermore, inhibition of recruitment of Fmn1 and/or Arp2/3 by deleting TarP was sufficient to similarly attenuated actin kinetics and invasion efficiency, supporting a model wherein TarP is the major contributor to robust actin remodeling via its recruitment of the two classes of actin nucleators. At the population level, the kinetics of recruitment and turnover of actin and its nucleators were linked. However, a more detailed analysis of the data at the level of individual elementary bodies showed significant variation and a lack of correlation between the kinetics of recruitment and turnover, suggesting that accessory factors variably modify actin kinetics at individual entry sites. In summary, efficient chlamydial invasion requires a specific profile of actin dynamics which are coordinated by TarP-dependent recruitment of two classes of actin nucleators.

scholarly journals Regulation of invasion-associated actin dynamics by the Chlamydia trachomatis effectors TarP and TmeA

2021 ◽  
Author(s):  
Matthew D. Romero ◽  
Rey A. Carabeo
Keyword(s):  
Chlamydia Trachomatis ◽  
Population Level ◽  
Actin Dynamics ◽  
Actin Remodeling ◽  
Obligate Intracellular ◽  
Core Components ◽  
Obligate Intracellular Pathogen ◽  
Pathogen Entry ◽  
Kinetics Of ◽  
Slow Turnover

The obligate intracellular pathogen  Chlamydia trachomatis manipulates the host actin cytoskeleton to assemble actin-rich structures that drive pathogen entry. This actin remodeling event exhibits relatively rapid dynamics that, through quantitative live-cell imaging, was revealed to consist of three phases – a fast recruitment phase which abruptly transitions to a fast turnover phase before resolving into a slow turnover of actin, indicating the end of actin remodeling. Here, we investigate Chlamydia invasion in the context of actin dynamics. Efficient invasion was associated with robust actin remodeling kinetics, which was linked to signaling from the type-III secreted effectors TarP and TmeA, and the actin nucleating activities of formin 1 (Fmn1) and Arp2/3. Stable recruitment of Fmn1 and Arp2/3 was dependent upon TarP and/or TmeA, although TarP signaling was responsible for the majority of Fmn1 and Arp2/3 recruitment. Rapid actin kinetics were due in part to a collaborative functional interaction between two different classes of actin nucleators – formins, including formin 1 and the diaphanous-related formins mDia1 and mDia2, and the Arp2/3 complex. Inhibition of either formin or Arp2/3, or deletion of TarP and TmeA, prevented this collaboration and resulted in attenuated actin kinetics and invasion efficiency. Collectively, these data support a model wherein TarP and TmeA signaling are core components of actin remodeling that operate via stable recruitment of formin and Arp2/3. At the population level, the kinetics of recruitment and turnover of actin and its nucleators were linked. However, reanalysis of the data at the level of individual elementary bodies showed significant variation and a lack of correlation between the kinetics of recruitment and turnover, suggesting that accessory factors variably modify actin kinetics at individual entry sites. In summary, efficient chlamydial invasion is an effector-driven process that requires a specific profile of actin recruitment which arises following collaboration between formin and Arp2/3.

scholarly journals MPK3- and MPK6-mediated VLN3 phosphorylation regulates actin dynamics during stomatal immunity in Arabidopsis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Minxia Zou ◽  
Mengmeng Guo ◽  
Zhaoyang Zhou ◽  
Bingxiao Wang ◽  
Qing Pan ◽  
...  
Keyword(s):  
Plant Immunity ◽  
Actin Dynamics ◽  
Innate Immune Responses ◽  
Genetic Studies ◽  
Actin Remodeling ◽  
Mitogen Activated Protein ◽  
Quantitative Analyses ◽  
Pathogen Entry

AbstractUpon perception of pathogens, plants can rapidly close their stomata to restrict pathogen entry into internal tissue, leading to stomatal immunity as one aspect of innate immune responses. The actin cytoskeleton is required for plant defense against microbial invaders. However, the precise functions of host actin during plant immunity remain largely unknown. Here, we report that Arabidopsis villin3 (VLN3) is critical for plant resistance to bacteria by regulating stomatal immunity. Our in vitro and in vivo phosphorylation assays show that VLN3 is a physiological substrate of two pathogen-responsive mitogen-activated protein kinases, MPK3/6. Quantitative analyses of actin dynamics and genetic studies reveal that VLN3 phosphorylation by MPK3/6 modulates actin remodeling to activate stomatal defense in Arabidopsis.

scholarly journals Analysis of Putative Chlamydia trachomatis Chaperones Scc2 and Scc3 and Their Use in the Identification of Type III Secretion Substrates

2005 ◽  
Vol 187 (18) ◽  
pp. 6466-6478 ◽  
Author(s):  
Kenneth A. Fields ◽  
Elizabeth R. Fischer ◽  
David J. Mead ◽  
Ted Hackstadt
Keyword(s):  
Chlamydia Trachomatis ◽  
Type Iii Secretion ◽  
Translocator Protein ◽  
Type Iii ◽  
Functional Studies ◽  
Infected Cells ◽  
Obligate Intracellular Pathogen ◽  
Insight Into

ABSTRACT The obligate intracellular pathogen Chlamydia trachomatis expresses a type III secretion system (T3SS) which has the potential to contribute significantly to pathogenesis. Based on a demonstrated role of type III secretion (T3S)-specific chaperones in the secretion of antihost proteins by gram-negative pathogens, we initiated a study of selected putative Chlamydia T3S chaperones in an effort to gain mechanistic insight into the Chlamydia T3SS and to potentially identify Chlamydia-specific secreted products. C. trachomatis Scc2 and Scc3 are homologous to SycD of Yersinia spp. Functional studies of the heterologous Yersinia T3SS indicated that although neither Scc2 nor Scc3 was able to fully complement a sycD null mutant, both have SycD-like characteristics. Both were able to associate with the translocator protein YopD, and Scc3 expression restored limited secretion of YopD in in vitro studies of T3S. CopB (CT578) and CopB2 (CT861) are encoded adjacent to scc2 and scc3, respectively, and have structural similarities with the YopB family of T3S translocators. Either Scc2 or Scc3 coprecipitates with CopB from C. trachomatis extracts. Expression of CopB or CopB2 in Yersinia resulted in their type III-dependent secretion, and localization studies with C. trachomatis-infected cells indicated that both were secreted by Chlamydia.

scholarly journals Chlamydia trachomatis Species-Specific Induction of Ezrin Tyrosine Phosphorylation Functions in Pathogen Entry

2007 ◽  
Vol 75 (12) ◽  
pp. 5669-5677 ◽  
Author(s):  
Kena A. Swanson ◽  
Deborah D. Crane ◽  
Harlan D. Caldwell
Keyword(s):  
Chlamydia Trachomatis ◽  
Host Cell ◽  
Tyrosine Phosphorylation ◽  
Mammalian Cells ◽  
Dominant Negative ◽  
Host Protein ◽  
Host Cells ◽  
Obligate Intracellular Pathogen ◽  
Pathogen Entry ◽  
Species Specific

ABSTRACT Chlamydia trachomatis is an obligate intracellular pathogen of humans that exhibits species-specific biological characteristics in its early interactions with host cells that are likely important to pathogenesis. One such characteristic is the tyrosine phosphorylation (Tyr-P) of an ∼70-kDa polypeptide that occurs only after infection of mammalian cells by human strains. We sought to identify this protein because of its potential significance to the pathogenesis of human chlamydial infections. Using an immunoproteomic approach we identified the host protein ezrin, a member of the ezrin-radixin-moesin (ERM) protein family that serves as a physical link between host cell receptors and the actin cytoskeleton. Confocal microscopy studies showed colocalization of ezrin and actin at the tips and crypts of microvilli, the site of chlamydial attachment and entry, respectively. To demonstrate a functional role for ezrin we infected cells with a dominant-negative (DN) ezrin phenotype or treated cells with ezrin-specific small interfering RNA (siRNA). We found that both DN and siRNA-treated cells were significantly less susceptible to infection by human chlamydial strains. Moreover, we demonstrated that inhibition of infection in ezrin DN cells occurred at the stage of chlamydial entry. We hypothesize that the C. trachomatis-specific Tyr-P of ezrin might relate to an undefined species-specific mechanism of pathogen entry that involves chlamydial specific ligand(s) and host cell coreceptor usage.

scholarly journals The Pseudomonas syringae Type III Effector HopG1 Induces Actin Remodeling to Promote Symptom Development and Susceptibility during Infection

2016 ◽  
Vol 171 (3) ◽  
pp. 2239-2255 ◽  
Author(s):  
Masaki Shimono ◽  
Yi-Ju Lu ◽  
Katie Porter ◽  
Brian H. Kvitko ◽  
Jessica Henty-Ridilla ◽  
...  
Keyword(s):  
Pseudomonas Syringae ◽  
Symptom Development ◽  
Actin Remodeling ◽  
Type Iii Effector ◽  
Type Iii
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