Format

Send to

Choose Destination
Mol Biol Cell. 2015 May 15;26(10):1918-34. doi: 10.1091/mbc.E14-11-1530. Epub 2015 Mar 18.

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

Author information

1
Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201.
2
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 20201.
3
Mass Spectrometry Center, University of Maryland School of Pharmacy, Baltimore, MD 21201.
4
Core Imaging Facility and Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD 21201.
5
Institute for Genome Science, University of Maryland School of Medicine, Baltimore, MD 20201.
6
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
7
Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201 pbavoil@umaryland.edu.

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.

PMID:
25788290
PMCID:
PMC4436835
DOI:
10.1091/mbc.E14-11-1530
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center