Abstract
Understanding how host proteins are targeted to pathogen-specified organelles, like the chlamydial inclusion, is fundamentally important to understanding the biogenesis of these unique subcellular compartments and how they maintain autonomy within the cell. Syntaxin 6, which localizes to the chlamydial inclusion, contains an YGRL signal sequence. The YGRL functions to return syntaxin 6 to the trans-Golgi from the plasma membrane, and deletion of the YGRL signal sequence from syntaxin 6 also prevents the protein from localizing to the chlamydial inclusion. YGRL is one of three YXXL (YGRL, YQRL, and YKGL) signal sequences which target proteins to the trans-Golgi. We designed various constructs of eukaryotic proteins to test the specificity and propensity of YXXL sequences to target the inclusion. The YGRL signal sequence redirects proteins (e.g., Tgn38, furin, syntaxin 4) that normally do not localize to the chlamydial inclusion. Further, the requirement of the YGRL signal sequence for syntaxin 6 localization to inclusions formed by different species of Chlamydia is conserved. These data indicate that there is an inherent property of the chlamydial inclusion, which allows it to recognize the YGRL signal sequence. To examine whether this “inherent property” was protein or lipid in nature, we asked if deletion of the YGRL signal sequence from syntaxin 6 altered the ability of the protein to interact with proteins or lipids. Deletion or alteration of the YGRL from syntaxin 6 does not appreciably impact syntaxin 6-protein interactions, but does decrease syntaxin 6-lipid interactions. Intriguingly, data also demonstrate that YKGL or YQRL can successfully substitute for YGRL in localization of syntaxin 6 to the chlamydial inclusion. Importantly and for the first time, we are establishing that a eukaryotic signal sequence targets the chlamydial inclusion.
Highlights
Depending on the mode of acquisition, C. trachomatis serovars cause several types of infections including blinding trachoma (Schachter, 1999), or the most common bacterially associated sexually transmitted infection (STI)
Recent studies demonstrated that only a single protein within Chlamydia is biotinylated (Fisher et al, 2012), which is consistent with the lack of structures being biotinylated by BirA∗-syntaxin 6 in the absence of exogenous biotin (Figure 1C)
The YGRL signal sequence recognizes inclusions formed by multiple species of Chlamydia, indicating that it is interacting with a conserved component that is integral to inclusion integrity or composition
Summary
Depending on the mode of acquisition, C. trachomatis serovars cause several types of infections including blinding trachoma (Schachter, 1999), or the most common bacterially associated sexually transmitted infection (STI). The infectious form, termed the elementary body (EB), is endocytosed into the host cell and remains membrane-bound in a vesicle which develops into a pathogenspecified organelle, known as the inclusion. The RB actively remodels the surrounding vacuolar membrane with secreted proteins (Fields et al, 2003). These early modifications to the inclusion correspond with the chlamydial acquisition of host-derived lipids (Hackstadt et al, 1996). The intracellular growth and division of Chlamydia within the inclusion is essential to the completion of the chlamydial development cycle which culminates in the release of infectious progeny (Ward, 1988). This study examines how eukaryotic proteins are targeted to this pathogen-specified organelle
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