Transcriptional and post-translational regulation of junctional adhesion molecule-B (JAM-B) in leukocytes under inflammatory stimuli

Day-Walsh, Priscilla, Keeble, Bryony, Pirabagar, Gothai, Fountain, Samuel ORCID: https://orcid.org/0000-0002-6028-0548 and Kroon, Paul (2022) Transcriptional and post-translational regulation of junctional adhesion molecule-B (JAM-B) in leukocytes under inflammatory stimuli. International Journal of Molecular Sciences, 23 (15). ISSN 1661-6596

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Abstract

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. View Full-Text

Item Type: Article
Additional Information: Funding Information: This research was funded by the BBSRC Institute Strategic Programme Food Innovation and Health BB/R012512/1 and its constituent projects BBS/E/F/000PR10343 and BBS/E/F/000PR10347. S.F. was funded by the British Heart Foundation, project grant PG/16/94/32393.
Uncontrolled Keywords: barrier function,cell adhesion,cell migration,cell permeability,host,inflammation,pathogen,tight junctions,catalysis,molecular biology,spectroscopy,computer science applications,physical and theoretical chemistry,organic chemistry,inorganic chemistry ,/dk/atira/pure/subjectarea/asjc/1500/1503
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 12 Oct 2022 14:33
Last Modified: 25 Oct 2022 13:33
URI: https://ueaeprints.uea.ac.uk/id/eprint/89012
DOI: 10.3390/ijms23158646

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