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UnknownThe signaling proteins GPR158 and RGS7 modulate excitability of L2/3 pyramidal neurons and control A-type potassium channel in the prelimbic cortex.
Stress profoundly affects physiological properties of neurons across brain circuits and thereby increases the risk for depression. However, the molecular and cellular mechanisms mediating these effects are poorly understood. In this study, we report that chronic physical restraint stress in mice dec...
S-EPMC6721952 | biostudies-literature
UnknownSynaptic adhesion protein ELFN1 is a selective allosteric modulator of group III metabotropic glutamate receptors in trans.
Functional characterization of the GPCR interactome has been focused predominantly on intracellular interactions, yet GPCRs are increasingly found in complex with extracellular proteins. Extracellular leucine-rich repeat fibronectin type III domain containing 1 (ELFN1) was recently reported to physi...
S-EPMC5948991 | biostudies-literature
UnknownAllostatic Changes in the cAMP System Drive Opioid-Induced Adaptation in Striatal Dopamine Signaling.
Opioids are powerful addictive agents that alter dopaminergic influence on reward signaling in medium spiny neurons (MSNs) of the nucleus accumbens. Repeated opioid exposure triggers adaptive changes, shifting reward valuation to the allostatic state underlying tolerance. However, the cellular subst...
S-EPMC6871051 | biostudies-literature
UnknownELFN2 is a postsynaptic cell adhesion molecule with essential roles in controlling group III mGluRs in the brain and neuropsychiatric behavior.
The functional characterization of the GPCR interactome has predominantly focused on intracellular binding partners; however, the recent emergence of transsynaptic GPCR complexes represents an additional dimension to GPCR function that has previously been unaccounted for in drug discovery. Here, we ...
S-EPMC6874751 | biostudies-literature
UnknownHomeostatic cAMP regulation by the RGS7 complex controls depression-related behaviors.
Affective disorders arise from abnormal responses of the brain to prolonged exposure to challenging environmental stimuli. Recent work identified the orphan receptor GPR158 as a molecular link between chronic stress and depression. Here we reveal a non-canonical mechanism by which GPR158 exerts its ...
S-EPMC6333837 | biostudies-literature
UnknownDiversity of the Gβγ complexes defines spatial and temporal bias of GPCR signaling.
The signal transduction by G-protein-coupled receptors (GPCRs) is mediated by heterotrimeric G proteins composed from one of the 16 Gα subunits and the inseparable Gβγ complex assembled from a repertoire of 5 Gβ and 12 Gγ subunits. However, the functional role of compositional diversity in Gβγ compl...
S-EPMC8068604 | biostudies-literature
UnknownOrphan Receptor GPR158 Is an Allosteric Modulator of RGS7 Catalytic Activity with an Essential Role in Dictating Its Expression and Localization in the Brain.
Regulators of G protein signaling control the duration and extent of signaling via G protein-coupled receptor (GPCR) pathways by accelerating the GTP hydrolysis on G protein α subunits thereby promoting termination of GPCR signaling. A member of this family, RGS7, plays a critical role in the nervou...
S-EPMC4447942 | biostudies-literature
UnknownDistinct profiles of functional discrimination among G proteins determine the actions of G protein-coupled receptors.
Members of the heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) family play key roles in many physiological functions and are extensively exploited pharmacologically to treat diseases. Many of the diverse effects of individual GPCRs on cellular physiology are tra...
S-EPMC4886239 | biostudies-literature
UnknownDopamine Receptor DAMB Signals via Gq to Mediate Forgetting in Drosophila.
Prior studies have shown that aversive olfactory memory is acquired by dopamine acting on a specific receptor, dDA1, expressed by mushroom body neurons. Active forgetting is mediated by dopamine acting on another receptor, Damb, expressed by the same neurons. Surprisingly, prior studies have shown t...
S-EPMC6168074 | biostudies-literature
UnknownMembers of the KCTD family are major regulators of cAMP signaling.
Cyclic adenosine monophosphate (cAMP) is a pivotal second messenger with an essential role in neuronal function. cAMP synthesis by adenylyl cyclases (AC) is controlled by G protein-coupled receptor (GPCR) signaling systems. However, the network of molecular players involved in the process is incompl...
S-EPMC8740737 | biostudies-literature
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