title: The Chlamydia pneumoniae Inclusion Membrane Protein Cpn1027 Interacts with Host Cell Wnt Signaling Pathway Regulator Cytoplasmic Activation/Proliferation-Associated Protein 2 (Caprin2).
abstract: We previously identified hypothetical protein Cpn1027 as a novel inclusion membrane protein that is unique to Chlamydia pneumoniae. In the current study, using a yeast-two hybrid screen assay, we identified host cell cytoplasmic activation/proliferation-associated protein 2 (Caprin2) as an interacting partner of Cpn1027. The interaction was confirmed and mapped to the C-termini of both Cpn1027 and Caprin2 using co-immunoprecipitation and GST pull-down assays. A RFP-Caprin2 fusion protein was recruited to the chlamydial inclusion and so was the endogenous GSK3β, a critical component of the β-catenin destruction complex in the Wnt signaling pathway. Cpn1027 also co-precipitated GSK3β. Caprin2 is a key regulator of the Wnt signaling pathway by promoting the recruitment of the β-catenin destruction complex to the cytoplasmic membrane in the presence of Wnt signaling while GSK3β is required for priming β-catenin for degradation in the absence of Wnt signaling. The Cpn1027 interactions with Caprin2 and GSK3β may allow C. pneumoniae to actively sequester the β-catenin destruction complex so that β-catenin is maintained even in the absence of extracellular Wnt activation signals. The maintained β-catenin can trans-activate Wnt target genes including Bcl-2, which may contribute to the chlamydial antiapoptotic activity. We found that the C. pneumoniae-infected cells were more resistant to apoptosis induction and the anti-apoptotic activity was dependent on β-catenin. Thus, the current study suggests that the chlamydial inclusion protein Cpn1027 may be able to manipulate host Wnt signaling pathway for enhancing the chlamydial anti-apoptotic activity.
authors.affiliation: Department of Microbiology & Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Rhonda
authors.initials: R
authors.lastname: Flores
authors.affiliation: Department of Microbiology & Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhong
mesh_terms: D017209:Apoptosis; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D016993:Chlamydophila pneumoniae / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D016601:RNA-Binding Proteins; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C486571:CAPRIN2 protein, human; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3