Transcriptional and Post-Translational Regulation of Junctional Adhesion Molecule-B (JAM-B) in Leukocytes under Inflammatory Stimuli

• Published in: International journal of molecular sciences 2022-08, Vol.23 (15), p.8646
• Main Authors: Day-Walsh, Priscilla E., Keeble, Bryony, Pirabagar, Gothai, Fountain, Samuel J., Kroon, Paul A.
• Format: Article
• Language: English
• Subjects: Adhesion; Amino acids; Anaphase; cell adhesion; cell migration; Cell permeability; Cytoplasm; Gene expression; Gene regulation; Golgi apparatus; Herpes simplex; host; Inflammation; Localization; NF-κB protein; pathogen; Pathogens; Physiology; Post-translation; Proteins; Signal transduction; Translation; Ubiquitin; Ubiquitin-protein ligase; Ubiquitin-specific proteinase; Ubiquitination
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23158646

Junctional adhesion molecules (JAMs; comprising JAM-A, -B and -C) act as receptors for viruses, mediate cell permeability, facilitate leukocyte migration during sterile and non-sterile inflammation and are important for the maintenance of epithelial barrier integrity. As such, they are implicated in the development of both communicable and non-communicable chronic diseases. Here, we investigated the expression and regulation of JAM-B in leukocytes under pathogen- and host-derived inflammatory stimuli using immunoassays, qPCR and pharmacological inhibitors of inflammatory signalling pathways. We show that JAM-B is expressed at both the mRNA and protein level in leukocytes. JAM-B protein is localised to the cytoplasm, Golgi apparatus and in the nucleus around ring-shaped structures. We also provide evidence that JAM-B nuclear localisation occurs via the classical importin-α/β pathway, which is likely mediated through JAM-B protein nuclear localisation signals (NLS) and export signals (NES). In addition, we provide evidence that under both pathogen- and host-derived inflammatory stimuli, JAM-B transcription is regulated via the NF-κB-dependent pathways, whereas at the post-translational level JAM-B is regulated by ubiquitin-proteosome pathways. Anaphase-promoting ubiquitin ligase complex (APC/C) and herpes simplex virus-associated ubiquitin-specific protease (HAUSP/USP) were identified as candidates for JAM-B ubiquitination and de-ubiquitination, respectively. The expression and regulation of JAM-B in leukocytes reported here is a novel observation and contrasts with previous reports. The data reported here suggest that JAM-B expression in leukocytes is under the control of common inflammatory pathways.