title: SINC, a type III secreted protein of Chlamydia psittaci, targets the inner nuclear membrane of infected cells and uninfected neighbors.
abstract: SINC, a new type III secreted protein of the avian and human pathogen Chlamydia psittaci, uniquely targets the nuclear envelope of C. psittaci-infected cells and uninfected neighboring cells. Digitonin-permeabilization studies of SINC-GFP-transfected HeLa cells indicate that SINC targets the inner nuclear membrane. SINC localization at the nuclear envelope was blocked by importazole, confirming SINC import into the nucleus. Candidate partners were identified by proximity to biotin ligase-fused SINC in HEK293 cells and mass spectrometry (BioID). This strategy identified 22 candidates with high confidence, including the nucleoporin ELYS, lamin B1, and four proteins (emerin, MAN1, LAP1, and LBR) of the inner nuclear membrane, suggesting that SINC interacts with host proteins that control nuclear structure, signaling, chromatin organization, and gene silencing. GFP-SINC association with the native LEM-domain protein emerin, a conserved component of nuclear "lamina" structure, or with a complex containing emerin was confirmed by GFP pull down. Our findings identify SINC as a novel bacterial protein that targets the nuclear envelope with the capability of globally altering nuclear envelope functions in the infected host cell and neighboring uninfected cells. These properties may contribute to the aggressive virulence of C. psittaci.
authors: Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201.
authors: Sergio A
authors: SA
authors: Mojica
authors: Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201.
authors: Kelley M
authors: KM
authors: Hovis
authors: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 20201.
authors: Matthew B
authors: MB
authors: Frieman
authors: Mass Spectrometry Center, University of Maryland School of Pharmacy, Baltimore, MD 21201.
authors: Bao
authors: B
authors: Tran
authors: Core Imaging Facility and Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD 21201.
authors: Ru-ching
authors: RC
authors: Hsia
authors: Institute for Genome Science, University of Maryland School of Medicine, Baltimore, MD 20201.
authors: Jacques
authors: J
authors: Ravel
authors: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors: Clifton
authors: C
authors: Jenkins-Houk
authors: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors: Katherine L
authors: KL
authors: Wilson
authors: Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201 pbavoil@umaryland.edu.
authors: Patrik M
authors: PM
authors: Bavoil
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D002691:Chlamydophila psittaci / Q000378:metabolism* / Q000472:pathogenicity; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D013058:Mass Spectrometry; D009685:Nuclear Envelope / Q000378:metabolism / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins