The trans-Golgi SNARE syntaxin 6 is recruited to the chlamydial inclusion membrane

Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories, 903 South 4th Street, Hamilton, MT 59840, USA.
Microbiology (Impact Factor: 2.56). 11/2010; 157(Pt 3):830-8. DOI: 10.1099/mic.0.045856-0
Source: PubMed


Chlamydia trachomatis is an obligate intracellular pathogen that replicates within a parasitophorous vacuole termed an inclusion. The chlamydial inclusion is isolated from the endocytic pathway but fusogenic with Golgi-derived exocytic vesicles containing sphingomyelin and cholesterol. Sphingolipids are incorporated into the chlamydial cell wall and are considered essential for chlamydial development and viability. The mechanisms by which chlamydiae obtain eukaryotic lipids are poorly understood but require chlamydial protein synthesis and presumably modification of the inclusion membrane to initiate this interaction. A polarized cell model of chlamydial infection has demonstrated that chlamydiae preferentially intercept basolaterally directed, sphingomyelin-containing exocytic vesicles. Here we examine the localization and potential function of trans-Golgi and/or basolaterally associated soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in chlamydia-infected cells. The trans-Golgi SNARE protein syntaxin 6 is recruited to the chlamydial inclusion in a manner that requires chlamydial protein synthesis and is conserved among all chlamydial species examined. The localization of syntaxin 6 to the chlamydial inclusion requires a tyrosine motif or plasma membrane retrieval signal (YGRL). Thus in addition to expression of at least two inclusion membrane proteins that contain SNARE-like motifs, chlamydiae also actively recruit eukaryotic SNARE-family proteins.

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    • "Chlamydia trachomatis is an obligate intracellular pathogen; syntaxin-6 has been shown to be involved in the formation of the parasitophorous vacuole, an inclusion that is required for replication of the pathogen. Host syntaxin-6 is recruited to the chlamydial inclusion membrane protein; although the exact function of syntaxin-6 at the inclusion membrane remains to be defined, it is believed that it may mediate specific vesicle fusion events required for maintaining the chlamydial inclusion [71]. Another intracellular pathogen Salmonella has been shown to acquire LAMP1 (lysosome-associated membrane protein 1) on phagosomes from the TGN via Salmonella effector protein-mediated recruitment of host syntaxin-6, probably to stabilize their niche in macrophages [72]. "
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    ABSTRACT: Intracellular membrane trafficking along endocytic and secretory transport pathways plays a critical role in diverse cellular functions including both developmental and pathological processes. Briefly, proteins and lipids destined for transport to distinct locations are collectively assembled into vesicles and delivered to their target site by vesicular fusion. SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) proteins are required for these events, during which v-SNAREs (vesicle SNAREs) interact with t-SNAREs (target SNAREs) to allow transfer of cargo from donor vesicle to target membrane. Recently, the t-SNARE family member, syntaxin-6, has been shown to play an important role in the transport of proteins that are key to diverse cellular dynamic processes. In this paper, we briefly discuss the specific role of SNAREs in various mammalian cell types and comprehensively review the various roles of the Golgi- and endosome-localized t-SNARE, syntaxin-6, in membrane trafficking during physiological as well as pathological conditions.
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    • "Interestingly, Rab14-positive vesicles are present within the lumen of the inclusion, suggesting that the inclusion may directly fuse with Rab14 vesicles containing SM. In addition to the recruitment of Rabs, Chlamydia may regulate fusion with host vesicles for delivery of essential lipids by recruiting Golgi-associated host soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) (Moore et al., 2011; Pokrovskaya et al., 2012), which are key components of intracellular fusion machinery, and/or expression of Inc proteins that contain SNARE-like motifs (Delevoye et al., 2008). Phosphoinositides are short-lived phosphorylated derivatives of PI that regulate the localization of PI-binding proteins and thus contribute to host cell lipid transport and signalling (D'Angelo et al., 2008). "
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    ABSTRACT: Chlamydia species are obligate intracellular pathogens that are important causes of human genital tract, ocular and respiratory infections. The bacteria replicate within a specialized membrane-bound compartment termed the inclusion and require host-derived lipids for intracellular growth and development. Emerging evidence indicates that Chlamydia has evolved clever strategies to fulfil its lipid needs by interacting with multiple host cell compartments and redirecting trafficking pathways to its intracellular niche. In this review, we highlight recent findings that have significantly expanded our understanding of how Chlamydia exploit lipid trafficking pathways to ensure the survival of this important human pathogen.
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    ABSTRACT: Chlamydia trachomatis is the causing agent of the most frequent bacterial sexually-transmitted diseases worldwide and is an underlying cause of chronic pelvic inflammatory diseases and cervical cancer. It is an obligate intracellular bacterium that establishes a close relationship with the Golgi complex and parasites the biosynthetic machinery of host cells. In a recent study, we have demonstrated that Rab14, a newly-described Golgi-associated Rab, is involved in the delivery of sphingolipids to the growing bacteria-containing vacuole. The interference with Rab14-controlled trafficking pathways delays chlamydial inclusion enlargement, decreases bacterial lipid uptake, negatively impact on bacterial differentiation, and reduces bacterial progeny and infectivity. C. trachomatis manipulation of host trafficking pathways for the acquisition of endogenously-biosynthesized nutrients arises as one of the characteristics of this highly evolved pathogen. The development of therapeutic strategies targeted to interfere with bacterium-host cell interaction is a new challenge for pharmacological approaches to control chlamydial infections.
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