Two-component system (TCS) signaling circuits regulate numerous cellular processes in response to environmental cues in both prokaryotic and eukaryotic cells. These signaling circuits are all based on phosphoryl-group transfers between histidine and aspartate containing modules of sensor kinase and response regulator proteins. Curiously, the architecture and organization of prokaryotic and eukaryotic two-component systems reveal notable variations, raising the question of whether the input-response specificity that governs the majority of prokaryotic TCSs also governs the eukaryotic ones. In this review, we contrast the TCS architecture and signaling circuits of prokaryotes and eukaryotes, and discuss their possible consequences on signaling specificity.
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http://dx.doi.org/10.1111/1462-2920.13397 | DOI Listing |
The mu-opioid receptor (MOR) is a major target for the treatment of pain. However, opioids are prone to side effects which limit their effectiveness as analgesics and can lead to opioid use disorders or, even, lethal overdose. The systemic administration of opioid agonists makes it both very difficult to decipher their underlying circuit mechanisms of action and to limit drug action to specific receptor subpopulations to isolate therapeutic effects from adverse side effects.
View Article and Find Full Text PDFFluorescent reporters for glutamate release and postsynaptic Ca signaling are essential tools for quantifying synapse functional heterogeneity across neurons and circuits. However, leveraging these probes for neuroscience requires scalable experimental frameworks. Here, we devised a high-throughput approach to efficiently collect and analyze hundreds of optical recordings of glutaamate release activity at presynaptic boutons in cultured rat hippocampal neurons.
View Article and Find Full Text PDFThe ability to observe the social behavior of others and use observed information to bias future action is a fundamental building block of social cognition . A foundational question is whether social observation and experience engage common circuit mechanisms that enable behavioral change. While classic studies on social learning have shown that aggressive behaviors can be learned through observation , it remains unclear whether aggression observation promotes persistent neural changes that generalize to new contexts.
View Article and Find Full Text PDFUnlabelled: Pain therapies that alleviate both pain and sleep disturbances may be the most effective for pain relief, as both chronic pain and sleep loss render the opioidergic system, targeted by opioids, less sensitive and effective for analgesia. Therefore, we first studied the link between sleep disturbances and the activation of nociceptors in two acute pain models. Activation of nociceptors in both acute inflammatory (AIP) and opto-pain models led to sleep loss, decreased sleep spindle density, and increased sleep fragmentation that lasted 3 to 6 hours.
View Article and Find Full Text PDFGlucagon-like peptide-1 receptor agonists (GLP1RAs) effectively reduce body weight and improve metabolic outcomes, yet established peptide-based therapies require injections and complex manufacturing. Small-molecule GLP1RAs promise oral bioavailability and scalable manufacturing, but their selective binding to human versus rodent receptors has limited mechanistic studies. The neural circuits through which these emerging therapeutics modulate feeding behavior remain undefined, particularly in comparison to established peptide-based GLP1RAs.
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