<scp>GPCR</scp>
            Signaling from Intracellular Membranes

Jong, Yuh-Jiin I.; Harmon, Steven K.; O’Malley, Karen L.

doi:10.1002/9781119564782.ch8

Cited by 3 publications

(5 citation statements)

References 332 publications

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“…The present study recovered the interconnections between cAMP signaling molecules listed in the STRING repository. The associations between DRD2, GIPR, DRD1, and SSTR5 in STRING and detected in this study are consistent with the participation of these molecules in G protein-coupled receptor signaling that plays a role in learning and memory and pain sensation [41]. The previous patterns agree with reports that the dopamine system in the hippocampus is overactive in patients diagnosed with MIA-related schizophrenia spectrum disorder [42].…”

Section: Camp Signaling Network Profiles Impacted By Maternal Immune ...supporting

confidence: 92%

Hippocampal Changes Elicited by Metabolic and Inflammatory Stressors following Prenatal Maternal Infection

Rodríguez-Zas

Southey

Rymut

et al. 2022

Genes

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The hippocampus participates in spatial navigation and behavioral processes, displays molecular plasticity in response to environmental challenges, and can play a role in neuropsychiatric diseases. The combined effects of inflammatory prenatal and postnatal challenges can disrupt the hippocampal gene networks and regulatory mechanisms. Using a proven pig model of viral maternal immune activation (MIA) matched to controls and an RNA-sequencing approach, the hippocampal transcriptome was profiled on two-month-old female and male offspring assigned to fasting, mimetic viral, or saline treatments. More than 2600 genes presented single or combined effects (FDR-adjusted p-value < 0.05) of MIA, postnatal stress, or sex. Biological processes and pathways encompassing messenger cyclic adenosine 3′,5′-monophosphate (cAMP) signaling were enriched with genes including gastric inhibitory polypeptide receptor (GIPR) predominantly over-expressed in the MIA-exposed fasting males relative to groups that differed in sex, prenatal or postnatal challenge. While this pattern was amplified in fasting offspring, the postnatal inflammatory challenge appeared to cancel out the effects of the prenatal challenge. The transcription factors C-terminal binding protein 2 (CTBP2), RE1 silencing transcription factor (REST), signal transducer and activator of transcription 1 (STAT1), and SUZ12 polycomb repressive complex 2 subunit were over-represented among the genes impacted by the prenatal and postnatal factors studied. Our results indicate that one environmental challenge can influence the effect of another challenge on the hippocampal transcriptome. These findings can assist in the identification of molecular targets to ameliorate the effects of pre-and post-natal stressors on hippocampal-associated physiology and behavior.

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Section: Camp Signaling Network Profiles Impacted By Maternal Immune ...supporting

confidence: 92%

Hippocampal Changes Elicited by Metabolic and Inflammatory Stressors following Prenatal Maternal Infection

Rodríguez-Zas

Southey

Rymut

et al. 2022

Genes

View full text Add to dashboard Cite

show abstract

“…Functionally, sustained intracellular GPCR signaling is often associated with long-term physiological processes. For example, sustained signaling following activation of many intracellular GPCRs can lead to increased transcription, proliferation, and cell survival ( 49 , 50 , 51 ). Prolonged mGlu 5 Ca 2+ signaling led to enhanced transcription particularly of synaptic plasticity genes ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we tabulated ∼120 GPCRs that exhibit compartmentalized signaling. Depending upon their intracellular location, compartmentalized GPCRS control functions such as transcription, proliferation, and survival, as well as metabolic, physiological processes, respiration, and apoptosis ( 49 , 50 , 51 ). While most of the details of these processes remain to be discovered, it makes sense that GPCRs, the master regulators of cellular function, maintain and regulate the complex spatial and temporal interactions occurring inside the cell as well as transmit signals from the outside.…”

Section: Discussionmentioning

confidence: 99%

Striatal mGlu5-mediated synaptic plasticity is independently regulated by location-specific receptor pools and divergent signaling pathways

Jong

Izumi

Harmon

et al. 2023

Journal of Biological Chemistry

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Section: Targeting Gpcrs From Inside the Cellmentioning

confidence: 99%

“…However, degrading untagged and endogenous GPCRs is an ambitious task, primarily due to the extracellular location of the receptor orthosteric binding site. Even if a GPCR is internalised to an intracellular compartment such as endosomes or the Golgi, the GPCR remains embedded in the lipid bilayer with its orthosteric binding site protected from the cytosol (Dores & Trejo, 2012; Jong et al, 2022). One logical solution to this problem is to design a PROTAC that can bind to the cytosolic face of a GPCR, as this region is accessible to the cytosolic E3 ligases that are tractable small‐molecule targets.…”

Section: Targeting Gpcrs From Inside the Cellmentioning

confidence: 99%

The application of targeted protein degradation technologies to G protein‐coupled receptors

Keen

Jörg

Halls

2023

British J Pharmacology

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The ubiquitin‐proteasome system is one of the major pathways for the degradation of cellular proteins. In recent years, methods have been developed to exploit the ubiquitin‐proteasome system to artificially degrade target proteins. Targeted protein degraders are extremely useful as biological tools for discovery research. They have also been developed as novel therapeutics with several targeted protein degraders currently in clinical trials. However, almost all targeted protein degrader technologies have been developed for cytosolic proteins. The G protein‐coupled receptor (GPCR) superfamily is one of the most important classes of drug targets, yet only limited examples of GPCR degradation exist. Here, we review these examples and provide a perspective on the different strategies that have been used to apply targeted protein degradation to GPCRs. We also discuss whether alternative approaches that have been used to degrade other integral membrane proteins could be applied to the degradation of GPCRs.

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GPCR Signaling from Intracellular Membranes

Cited by 3 publications

References 332 publications

Hippocampal Changes Elicited by Metabolic and Inflammatory Stressors following Prenatal Maternal Infection

Hippocampal Changes Elicited by Metabolic and Inflammatory Stressors following Prenatal Maternal Infection

Striatal mGlu5-mediated synaptic plasticity is independently regulated by location-specific receptor pools and divergent signaling pathways

The application of targeted protein degradation technologies to G protein‐coupled receptors

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