The Role of RNF216 in Neuroinflammation

Dustin Grossman, Dr. Angela Mabb, Neuroscience Institute, Georgia State University, Atlanta, GA 30302

Ubiquitin E3 ligases are enzymes that mark substrates with ubiquitin proteins which leads to different cellular fates. Ring finger protein 216 (RNF216) is a ubiquitin E3 ligase in the nervous system that is involved in synaptic plasticity, inhibiting cellular autophagy, and the immune response.  Previous literature shows that RNF216 participates in inflammation by regulating ubiquitination and proteasomal degradation of receptor-interacting serine-threonine kinase 1 (RIPK1), toll-interleukin 1 receptor domain-containing adaptor protein (TIRAP), and TIR-domain-containing adapter-inducing interferon-β (TRIF), targeting TNF receptor-associated factor 3 (TRAF3) for degradation. TLRs initiate signal transduction pathways which can lead to cytokine production, proliferation, survival, adaptive immunity, phagocytosis, and apoptosis.  One of the RNF216 isoforms, TRIAD3A, controls the intensity and duration of TLR signaling, specifically TLR4 and TLR9, through ubiquitination and subsequent proteolytic degradation. The role of RNF216 in the regulation of the factors that contribute to inflammation is not well studied in the central nervous system (CNS). Therefore, the goal of this work is to examine the extent to which the degradation of TLRs by RNF216 is involved in neuroinflammatory pathways. To study the role of RNF216 in these pathways, we used a mouse hypothalamic cell line (GT1-7) where Rnf216 was knocked down using the Crispr-Cas9 system. Using real-time quantitative polymerase chain reaction (RT-qPCR), we measured the expression of receptors and cytokines that regulate neuroinflammation. Our findings elucidate how disruptions in RNF216 may alter neuroinflammatory pathways.

Additional Abstract Information

Presenter: Dustin Grossman

Institution: Georgia State University

Type: Poster

Subject: Biology

Status: Approved

Time and Location

Session: Poster 2
Date/Time: Mon 3:00pm-4:00pm
Session Number: 2661