SINC, a type III secreted protein of <i>Chlamydia psittaci,</i> targets the inner nuclear membrane of infected cells and uninfected neighbors

Mojica, Sergio; Hovis, Kelley M.; Frieman, Matthew B.; Tran, Bao; Hsia, Ru Ching; Ravel, Jacques; Jenkins-Houk, Clifton; Wilson, Katherine L.; Bavoil, Patrik M.

doi:10.1091/mbc.e14-11-1530

Cited by 60 publications

(67 citation statements)

References 124 publications

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“…CPAF was initially described as a chlamydial protease degrading host cell transcription factors; however, its impact on virulence and pathogenicity is currently controversially discussed (20). SINC is a type III secreted protein targeting the nuclear membrane of infected cells, which may modulate the nuclear envelope function (10,11). Here, we have demonstrated that virulence-associated antibodies are generated predominantly in animals that have aborted.…”

Section: Discussionmentioning

confidence: 78%

“…From these, we have selected nine proteins for recombinant synthesis and further evaluation. These comprised (i) three surface proteins, specifically, the major outer membrane protein (MOMP), macrophage infectivity potentiator (MIP), and Pmp13G; (ii) three virulence-associated proteins, namely, the homologs of Chlamydia protease-like activity factor (CPAF), translocated actin-recruiting phosphoprotein (TARP), and secreted inner nuclear membrane-associated Chlamydia protein (SINC) (11), and (iii) three hypothetical proteins, specifically, CAB031, CAB821, and CAB408, two of which (CAB821 and CAB408) are predicted to be secreted by the type III secretion system (12). For a comprehensive analysis of the ovine and human antibody responses to these antigens, we used the so-called line immunoassay since this format allows the simultaneous detection of antibodies to multiple antigens in a single run (13).…”

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confidence: 99%

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Analysis of Humoral Immune Responses to Surface and Virulence-Associated Chlamydiaabortus Proteins in Ovine and Human Abortions by Use of a Newly Developed Line Immunoassay

et al. 2016

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fThe obligate intracellular bacterium Chlamydia abortus is the causative agent of enzootic abortion of ewes and poses a significant zoonotic risk for pregnant women. Using proteomic analysis and gene expression library screening in a previous project, we identified potential virulence factors and candidates for serodiagnosis, of which nine were scrutinized here with a strip immunoassay. We have shown that aborting sheep exhibited a strong antibody response to surface (MOMP, MIP, Pmp13G) and virulence-associated (CPAF, TARP, SINC) antigens. While the latter disappeared within 18 weeks following abortion in a majority of the animals, antibodies to surface proteins persisted beyond the duration of the study. In contrast, nonaborting experimentally infected sheep developed mainly antibodies to surface antigens (MOMP, MIP, Pmp13G), all of which did not persist. We were also able to detect antibodies to these surface antigens in C. abortus-infected women who had undergone septic abortion, whereas a group of shepherds and veterinarians with occupational exposure to C. abortus-infected sheep revealed only sporadic immune responses to the antigens selected. The most specific antigen for the serodiagnosis of human C. abortus infections was Pmp13G, which showed no cross-reactivity with other chlamydiae infecting humans. We suggest that Pmp13G-based serodiagnosis accomplished by the detection of antibodies to virulence-associated antigens such as CPAF, TARP, and SINC may improve the laboratory diagnosis of human and animal C. abortus infections. Chlamydia abortus is an obligate intracellularly replicating zoonotic bacterium that shares a characteristic biphasic developmental cycle with all other members of the family Chlamydiaceae (1). Among chlamydiae affecting humans, Chlamydia trachomatis is the most clinically and epidemiologically relevant as a cause of oculogenital infections, including nongonococcal urethritis and cervicitis, lymphogranuloma venereum, and trachoma. Chlamydia pneumoniae is known to be involved in community-acquired pneumonia, pharyngitis, bronchitis, and sinusitis. In addition, the avian pathogen Chlamydia psittaci has well-documented zoonotic potential, causing human psittacosis (ornithosis), which may present as a generalized and life-threatening pneumonia (2).C. abortus typically occurs in ruminants such as sheep and goats and is the leading cause of enzootic abortion of ewes (EAE) worldwide (3). Even in the absence of elevated abortion rates, the agent was shown to be widespread in German sheep flocks, with 50% of flocks testing PCR positive and 94% harboring seropositive animals (4). Afterbirths and fetuses of abortion cases can contain heavy loads of the pathogen and represent the major source of transmission to susceptible humans and naive ewes, as well as environmental contamination (3). Inhalation of infective aerosols by pregnant women poses the risk of severe infection, including spontaneous abortion, stillbirth, and septicemia (3, 5, 6). However, very little is known about the clinical rel...

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Section: Discussionmentioning

confidence: 78%

mentioning

confidence: 99%

Analysis of Humoral Immune Responses to Surface and Virulence-Associated Chlamydiaabortus Proteins in Ovine and Human Abortions by Use of a Newly Developed Line Immunoassay

et al. 2016

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“…BioID samples were processed for mass spectrometry as outlined by (27). Briefly, streptavidin beads were washed with 50 mM NH 4 HCO 3 and resuspended in 50 mM NH 4 HCO 3 containing 5 mM dithiothreitol and heated at 75°C for 10 min.…”

Section: Methodsmentioning

confidence: 99%

The basic tilted helix bundle domain of the prolyl isomerase FKBP25 is a novel double-stranded RNA binding module

Dilworth¹,

Upadhyay²,

Bonnafous³

et al. 2017

Nucleic Acids Research

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Prolyl isomerases are defined by a catalytic domain that facilitates the cis–trans interconversion of proline residues. In most cases, additional domains in these enzymes add important biological function, including recruitment to a set of protein substrates. Here, we report that the N-terminal basic tilted helix bundle (BTHB) domain of the human prolyl isomerase FKBP25 confers specific binding to double-stranded RNA (dsRNA). This binding is selective over DNA as well as single-stranded oligonucleotides. We find that FKBP25 RNA-association is required for its nucleolar localization and for the vast majority of its protein interactions, including those with 60S pre-ribosome and early ribosome biogenesis factors. An independent mobility of the BTHB and FKBP catalytic domains supports a model by which the N-terminus of FKBP25 is anchored to regions of dsRNA, whereas the FKBP domain is free to interact with neighboring proteins. Apart from the identification of the BTHB as a new dsRNA-binding module, this domain adds to the growing list of auxiliary functions used by prolyl isomerases to define their primary cellular targets.

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“…When Hela cells are infected by C. psittaci, SINC incorporates into the NE of the host cell nucleus and interacts with Nups, ELYS, lamin B1, and emerin, leading to alterations in nuclear shape and function in both infected cells and neighboring uninfected cells. 194 Many diseases are associated with altered nuclear morphology, so identifying approaches to correct these morphological defects may lead to novel therapeutics.…”

Section: Nuclear Morphology and Diseasementioning

confidence: 99%

Recent advances in understanding nuclear size and shape

Mukherjee

Chen

Levy

2016

Nucleus

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Size and shape are important aspects of nuclear structure. While normal cells maintain nuclear size within a defined range, altered nuclear size and shape are associated with a variety of diseases. It is unknown if altered nuclear morphology contributes to pathology, and answering this question requires a better understanding of the mechanisms that control nuclear size and shape. In this review, we discuss recent advances in our understanding of the mechanisms that regulate nuclear morphology, focusing on nucleocytoplasmic transport, nuclear lamins, the endoplasmic reticulum, the cell cycle, and potential links between nuclear size and size regulation of other organelles. We then discuss the functional significance of nuclear morphology in the context of early embryonic development. Looking toward the future, we review new experimental approaches that promise to provide new insights into mechanisms of nuclear size control, in particular microfluidic-based technologies, and discuss how altered nuclear morphology might impact chromatin organization and physiology of diseased cells.

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SINC, a type III secreted protein of Chlamydia psittaci, targets the inner nuclear membrane of infected cells and uninfected neighbors

Cited by 60 publications

References 124 publications

Analysis of Humoral Immune Responses to Surface and Virulence-Associated Chlamydiaabortus Proteins in Ovine and Human Abortions by Use of a Newly Developed Line Immunoassay

Analysis of Humoral Immune Responses to Surface and Virulence-Associated Chlamydiaabortus Proteins in Ovine and Human Abortions by Use of a Newly Developed Line Immunoassay

The basic tilted helix bundle domain of the prolyl isomerase FKBP25 is a novel double-stranded RNA binding module

Recent advances in understanding nuclear size and shape

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