Biology subjects

Downing, G.

Publications and source records attributed to Downing, G..

2 recordsLinked to original sources

bioRxiv2023

Cell autonomous regulation of the activation of AgRP neurons by the melanocortin-3 receptor

The melanocortin-3 receptor (MC3R) is a negative regulator of the central melanocortin circuitry via presynaptic expression on AgRP nerve terminals, from where it regulates GABA release onto secondary MC4R-expressing neurons. Hence, animals lacking MC3R (MC3R KO) exhibit hypersensitivity to MC4R agonists. However, MC3R KO mice also exhibit defective behavioral and neuroendocrine responses to fasting. Here, we demonstrate that MC3R KO mice exhibit defective activation of AgRP neurons in response to fasting and cold exposure, while exhibiting normal inhibition of AgRP neurons by sensory detection of food. Further, using an AgRP-specific MC3R knockout model, we show that the control of AgRP neuron activation by MC3R is cell-autonomous. One mechanism underlying this involves the response to ghrelin, which is also blunted in mice with AgRP-specific deletion of the MC3R. Thus, MC3R is a crucial player in the control of energy homeostasis by the central melanocortin system, not only acting presynaptically on AgRP neurons, but via AgRP cell-autonomous regulation of fasting- and cold-induced neuronal activation as well.

neuroscience↗

bioRxiv2020

Bacterial quorum sensing signal arrests phytoplankton cell division and protects against virus-induced mortality

Interactions between phytoplankton and heterotrophic bacteria fundamentally shape marine ecosystems. These interactions are driven by the exchange of compounds, however, linking these chemical signals, their mechanisms of action, and resultant ecological consequences remains a fundamental challenge. The bacterial signal 2-heptyl-4-quinolone (HHQ), induces immediate cellular stasis in the coccolithophore, Emiliania huxleyi, however, the mechanism responsible remains unknown. Here, we show that HHQ exposure leads to the accumulation of DNA damage in phytoplankton and prevents its repair. While this effect is reversible, HHQ-exposed phytoplankton are also protected from viral mortality, ascribing a new role of quorum sensing signals in regulating multi-trophic interactions. Further results demonstrate global HHQ production potential and the first in situ measurements of HHQ which coincide with areas of enhanced micro- and nanoplankton biomass. Our results support bacterial communication signals as emerging players, providing a new mechanistic framework for how compounds may contribute to structure complex marine microbial communities.

microbiology↗