CD82 controls CpG‐dependent TLR9 signaling

Khan, Nida S.; Lukason, Daniel P; Feliu, Marianela; Ward, Rebecca; Lord, Allison; Reedy, Jennifer L.; Ramirez-Ortiz, Zaida G.; Tam, Jenny M.; Kasperkovitz, Pia V.; Negoro, Paige; Vyas, Tammy D.; Xu, Shuying; Brinkmann, Melanie M.; Acharaya, Mridu; Artavanis‐Tsakonas, Katerina; Frickel, Eva‐Maria; Becker, Christine; Dagher, Zeina; Kim, You-Me; Latz, Eicke; Ploegh, Hidde L.; Mansour, Michael K.; Miranti, Cindy K.; Levitz, Stuart M.; Vyas, Jatin M.

doi:10.1096/fj.201901547r

Cited by 19 publications

(15 citation statements)

References 70 publications

(146 reference statements)

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“…Whereas TASL and TREML4 positively impact the signalling of multiple NA-sensing TLRs, there is one reported example of a signalling regulator that might be specific for TLR9. CD82, a transmembrane protein, positively regulates TLR9 signalling by promoting myddosome assembly 112,113 . In each of these cases, much more work is needed to understand the precise mechanisms by which these proteins control the signalling of NA-sensing TLRs.…”

Section: Signal Transductionmentioning

confidence: 99%

Regulation of the nucleic acid-sensing Toll-like receptors

et al. 2021

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Many of the ligands for Toll-like receptors (TLRs) are unique to microorganisms, such that receptor activation unequivocally indicates the presence of something foreign. However, a subset of TLRs recognizes nucleic acids, which are present in both the host and foreign microorganisms. This specificity enables broad recognition by virtue of the ubiquity of nucleic acids but also introduces the possibility of self-recognition and autoinflammatory or autoimmune disease. Defining the regulatory mechanisms required to ensure proper discrimination between foreign and self-nucleic acids by TLRs is an area of intense research. Progress over the past decade has revealed a complex array of regulatory mechanisms that ensure maintenance of this delicate balance. These regulatory mechanisms can be divided into a conceptual framework with four categories: compartmentalization, ligand availability, receptor expression and signal transduction. In this Review, we discuss our current understanding of each of these layers of regulation.

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Section: Signal Transductionmentioning

confidence: 99%

Regulation of the nucleic acid-sensing Toll-like receptors

et al. 2021

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“…The ability of KAI1 to suppress oncogenesis is linked to its ability to inhibit the expression of AP-1, JUNB, poly (ADP-ribose) polymerase (PARP) and other oncogenes ( 43 ). Khan et al ( 44 ) reported that KAI1 is a key regulator of Toll-like receptor 9 (TLR9) trafficking and signaling. KAI1 modulates TLR9-dependent NF-κB nuclear translocation, which is critical for inflammatory cytokine production.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑633 enhances melanoma cell proliferation and migration by suppressing KAI1

Wang

Liu

2020

Oncol Lett

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The aim of the present study was to determine the impact of microRNA (miRNA/miR)-633 on the biological properties of malignant melanoma cells. Kang-Ai 1 (KAI1), also known as cluster of differentiation 82, is an important transcriptional regulator and tumor suppressor gene present in different types of tumors. miRNAs that potentially bind with KAI1 were predicted via bioinformatics analyses. In total, six putative miRNA regulators of KAI1 were identified in the present analysis, among which miR-633 was upregulated the most in melanoma tissues compared with the control group. The expression levels of miR-633 and KAI1 in melanoma tissues compared with adjacent normal tissues were then assessed. It was found that miR-633 was significantly upregulated in melanoma cells compared with the control group, whereas the expression levels of KAI1 showed the opposite results. miR-633 was predicted to target the 3′-untranslated region of KAI1 using predictive online tools, and results from luciferase reporter assays confirmed the direct regulation of KAI1 promoter activity by miR-633. Furthermore, miR-633 mimics over expression was shown to suppress both mRNA and protein expression of KAI1, while miR-633 inhibition resulted in decreased viability and migrationin melanoma cells in vitro . Taken together, the present study demonstrated, to the best of the authors' knowledge for the first time, that miR-633 exerts an important role in melanoma through targeting KAI1.

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“…MCs express different receptors involved in the recognition of viral RNAs—Toll-like receptors (TLRs), retinoic acid-inducible gene 1 (RIG-1), and melanoma differentiation-associated gene 5 (MDA5) [ 101 , 102 ]. Khan et al recently characterized CD82 as the TLR9 interacting partner in macrophages [ 103 ]. Association of CD82 and TLR9 takes place in ER.…”

Section: Tetraspanins In Regulation Of MC Antiviral Responsementioning

confidence: 99%

Tetraspanins in the regulation of mast cell function

Orinska

Hagemann

Hálová

et al. 2020

Med Microbiol Immunol

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Mast cells (MCs) are long-living immune cells highly specialized in the storage and release of different biologically active compounds and are involved in the regulation of innate and adaptive immunity. MC degranulation and replacement of MC granules are accompanied by active membrane remodelling. Tetraspanins represent an evolutionary conserved family of transmembrane proteins. By interacting with lipids and other membrane and intracellular proteins, they are involved in organisation of membrane protein complexes and act as “molecular facilitators” connecting extracellular and cytoplasmic signaling elements. MCs express different tetraspanins and MC degranulation is accompanied by changes in membrane organisation. Therefore, tetraspanins are very likely involved in the regulation of MC exocytosis and membrane reorganisation after degranulation. Antiviral response and production of exosomes are further aspects of MC function characterized by dynamic changes of membrane organization. In this review, we pay a particular attention to tetraspanin gene expression in different human and murine MC populations, discuss tetraspanin involvement in regulation of key MC signaling complexes, and analyze the potential contribution of tetraspanins to MC antiviral response and exosome production. In-depth knowledge of tetraspanin-mediated molecular mechanisms involved in different aspects of the regulation of MC response will be beneficial for patients with allergies, characterized by overwhelming MC reactions.

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CD82 controls CpG‐dependent TLR9 signaling

Cited by 19 publications

References 70 publications

Regulation of the nucleic acid-sensing Toll-like receptors

Regulation of the nucleic acid-sensing Toll-like receptors

MicroRNA‑633 enhances melanoma cell proliferation and migration by suppressing KAI1

Tetraspanins in the regulation of mast cell function

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