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Subcellular location defines GPCR signal transduction

ABSTRACT: G protein-coupled receptors in intracellular organelles can be activated in response to membrane permeant ligands, which contributes to the diversity and specificity of agonist action. The opioid receptors (ORs) provide a striking example, where small molecule opioid drugs activate ORs in the Golgi apparatus within seconds of drug addition. To date, our knowledge on the signaling of intracellular GPCRs remains incomplete and it is unknown if the downstream events triggered by ORs in plasma membrane and Golgi apparatus differ. To address this gap, we analyzed OR-mediated phosphorylation changes in cells treated with SNC80 (signaling control) or ICI-SNC80 (Golgi-restricted signaling) for 5 min or 25 min. We show that OR activation in the plasma membrane or Golgi apparatus have strikingly different downstream effects on protein phosphorylation. The study delineates OR signal transduction with unprecedented resolution and reveals that the subcellular location defines the signaling effect promoted by opioid drugs.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Embryonic Cell

SUBMITTER: Lucie Oberhauser

LAB HEAD: Miriam Stoeber

PROVIDER: PXD038921 | Pride | 2023-04-25

REPOSITORIES: Pride

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			Action	DRS
	20200121_LU50HMC07_pl20004_LOberhauser_13_fractions_percolator.mgf	Mgf
	20200121_LU50HMC07_pl20004_LOberhauser_13_fractions_percolator.mzML	Mzml
	20200121_LU50HMC07_pl20004_LOberhauser_13_fractions_percolator.mzid.gz	Mzid
	20200121_LU50HMC07_pl20004_LOberhauser_P.raw	Raw
	20200121_LU50HMC07_pl20004_LOberhauser_P_percolator_1pep.mgf	Mgf

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Subcellular location defines GPCR signal transduction

Project description:G protein-coupled receptors in intracellular organelles can be activated in response to membrane permeant ligands, which contributes to the diversity and specificity of agonist action. The opioid receptors (ORs) provide a striking example, where small molecule opioid drugs activate ORs in the Golgi apparatus within seconds of drug addition. To date, our knowledge on the signaling of intracellular GPCRs remains incomplete and it is unknown if the downstream events triggered by ORs in plasma membrane and Golgi apparatus differ. To address this gap, we analyzed OR-mediated gene expression changes upon treatment with impermeant peptide ligand DPDPE, permeant ligand SNC80 or ICI-SNC80 (Golgi-restricted signaling). We show that DOR activation in the Golgi does not trigger any gene transcription at these two time points as compare to plasma membrane receptors. The study delineates OR signal transduction with unprecedented resolution and reveals that the subcellular location defines the signaling effect promoted by opioid drugs.

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