Biology subjects

Wang, A. R.

Publications and source records attributed to Wang, A. R..

3 recordsLinked to original sources

bioRxiv2023

SCFFBXW11 complex targets interleukin-17 receptor A for ubiquitin-proteasome-mediated degradation.

Interleukin-17 (IL-17) is a pro-inflammatory cytokine, participating in innate and adaptive immune responses, that plays an important role in host defense, autoimmune diseases, tissue regeneration, metabolic regulation, and tumor progression. Post-translational modifications (PTMs) are crucial for protein function, stability, cellular localization, cellular transduction, and cell death. However, PTMs of IL-17 receptor A (IL-17RA) have not been investigated. Here, we showed that human IL-17RA was targeted by F-box and WD repeats domain containing 11 (FBXW11) for ubiquitination, followed by proteasome-mediated degradation. We used bioinformatics tools and biochemical techniques to determine that FBXW11 ubiquitinated IL-17RA through a lysine 27-linked polyubiquitin chain, targeting IL-17RA for proteasomal degradation. Domain 665-804 of IL-17RA was critical for interaction with FBXW11 and subsequent ubiquitination. Our study demonstrates that FBXW11 regulates IL-17 signaling pathways at IL-17RA level.

biochemistry↗

bioRxiv2022

Striatal dopamine integrates cost, benefit and motivation

Dopamine (DA) release in the ventral and dorsal striatum has been linked to reward processing and motivation, but there are longstanding controversies about whether DA release in these key target structures primarily reflects costs or benefits, and how these signals vary with motivation. Here we apply behavioral economic principles to generate demand curves for rewards while directly measuring DA release in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) via a genetically-encoded sensor. By independently varying costs and benefits, we reveal that DA release in both structures incorporates reward magnitude and sunk cost. Surprisingly, motivation was inversely correlated with reward-evoked DA release; the higher the motivation for rewards the lower the reward-evoked DA release. These relationships between DA release, cost and motivation remained identical when we used optogenetic activation of striatal DA inputs as a reward. Our results reconcile previous disparate findings by demonstrating that during operant tasks, striatal DA release simultaneously encodes cost, benefit and motivation but in distinct manners over different time scales.

neuroscience↗

bioRxiv2021

Gpnmb inhibits oligodendrocyte differentiation of adult neural stem cells by amplifying TGFβ1 signaling

Gli1 expressing neural stem cells, in the subventricular zone of the adult mammalian brain, respond to demyelination injury by differentiating into oligodendrocytes. We have identified Gpnmb as a novel regulator of oligodendrogenesis in Gli1 neural stem cells, whose expression is induced by TGF{beta}1 signaling via Gli1, in response to a demyelinating injury. Upregulation of Gpnmb further activates the TGF{beta}1 pathway by increasing the expression of the TGF{beta}1 binding receptor subunit, TGF{beta}R2. Thus the TGF{beta}1[->]Gli1[->]Gpnmb[->]TGF{beta}R2 signaling pathway forms a feed forward loop for sustained activation of TGF{beta}1 signaling in Gli1 neural stem cells, resulting in inhibition of their differentiation into mature oligodendrocytes following demyelination.

neuroscience↗