Related Experiment Video

Updated: Oct 29, 2025

Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay
11:49

Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay

Published on: July 28, 2014

41.1K

The Orphan GPCR Receptor, GPR88, Interacts with Nuclear Protein Partners in the Cerebral Cortex

Florian Rebeillard, Stéphanie De Gois, Nicolas Pietrancosta

    Cerebral Cortex (New York, N.Y. : 1991)
    |July 11, 2021
    PubMed

    Insights

    G-protein-coupled receptor 88 (GPR88) exhibits atypical nuclear localization in cortical neurons, interacting with chromatin remodeling proteins. This finding suggests novel nonclassical functions for GPR88 in neuronal development.

    Area of Science:

    • Neuroscience
    • Molecular Biology
    • Cell Biology

    Background:

    • G-protein-coupled receptor 88 (GPR88) is highly expressed in striatal medium spiny neurons (MSN) and at lower levels in cortical neurons.
    • GPR88 displays canonical plasma membrane localization in MSN but atypical intranuclear localization in cortical neurons.
    • The full-length GPR88 protein is observed in both plasma membrane (MSN) and nuclear (cortical neurons) compartments.

    Purpose of the Study:

    • To investigate the atypical intranuclear localization of GPR88 in cortical neurons.
    • To identify the protein partners of GPR88 within the nucleus.
    • To explore potential nonclassical functions of GPR88 in neocortical neuron maturation.

    Main Methods:

    • Transfection of cortical neurons with GPR88 fluorescent chimeras.
    • Yeast two-hybrid screening using GPR88 intracytoplasmic loop and C-terminus domains.
    • Proximity ligation assay and co-immunoprecipitation experiments in cultured cortical neurons and mouse brain extracts.

    Main Results:

    • GPR88 fluorescent chimeras showed nuclear localization in transfected cortical neurons.
    • Nuclear localization was dependent on the third intracytoplasmic loop and C-terminus domains, despite lacking canonical nuclear localization signals.
    • Yeast two-hybrid screening identified ATRX, TOP2B, and BAZ2B, chromatin remodeling proteins, as potential GPR88 interactors.
    • Interaction between GPR88 and these nuclear proteins was validated in cortical neurons and mouse brain extracts.

    Conclusions:

    • GPR88 exhibits an atypical intranuclear localization in cortical neurons, mediated by specific protein domains.
    • GPR88 interacts with nuclear proteins involved in chromatin remodeling, including ATRX, TOP2B, and BAZ2B.
    • These findings suggest novel, nonclassical roles for GPR88 in nuclear functions, potentially impacting neocortical neuron maturation.
    Keywords:
    GPCRGPR88cerebral cortexnuclear proteinsprotein interaction

    More Related Videos

    A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 406:56

    A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4

    Published on: March 10, 2018

    14.0K
    Modified Yeast-Two-Hybrid System to Identify Proteins Interacting with the Growth Factor Progranulin07:56

    Modified Yeast-Two-Hybrid System to Identify Proteins Interacting with the Growth Factor Progranulin

    Published on: January 17, 2012

    28.9K

    Related Concept Videos

    G Protein-coupled Receptors01:15

    G Protein-coupled Receptors

    G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
    GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
    14.4K
    Transducer Mechanism: G Protein–Coupled Receptors01:30

    Transducer Mechanism: G Protein–Coupled Receptors

    G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
    GPCRs are also called heptahelical,...
    3.0K
    G-protein Coupled Receptors01:21

    G-protein Coupled Receptors

    G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
    126.2K
    GPCR Desensitization01:12

    GPCR Desensitization

    G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
    6.9K
    GPCRs Regulate Adenylyl Cylase Activity01:09

    GPCRs Regulate Adenylyl Cylase Activity

    Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
    6.2K
    Assembly of Signaling Complexes01:30

    Assembly of Signaling Complexes

    Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
    Interaction domains in cell signaling
    Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
    6.1K