Agonist-dependent delivery of M2 muscarinic acetylcholine receptors to the cell surface after pertussis toxin treatment

Aaron G. Roseberry, Moritz Bünemann, Jyoti T. Elavunkal, M. Marlene Hosey

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The internalization of the M2 muscarinic cholinergic receptor (mAChR) proceeds through an atypical pathway that is independent of arrestin and clathrin function and shows a unique sensitivity to dynamin when the receptor is expressed in human embryonic kidney 293 cells. In this report we demonstrate that the internalization of the M2 mAChR was modulated by activation of heterotrimeric G proteins, because treatment with pertussis toxin, which ADP-ribosylates G proteins of the Gi/o family, caused a significant delay in the onset of internalization of the M2 mAChR. The effects of pertussis toxin could not be explained by alteration of the agonist-dependent phosphorylation of the M2 mAChR. The modulation of internalization by pertussis toxin was revealed to be due to recruitment of intracellular receptors to the cell surface upon agonist treatment. Pretreatment with pertussis toxin also greatly increased both the rate and extent of recovery of M2 mAChRs to the cell surface after agonist-mediated internalization. These results demonstrate a novel aspect involved in the regulation of GPCRs. As with the tightly controlled internalization of GPCRs, the delivery of GPCRs to the cell surface is also highly regulated.

Original languageEnglish (US)
Pages (from-to)1256-1268
Number of pages13
JournalMolecular Pharmacology
Volume59
Issue number5
StatePublished - 2001
Externally publishedYes

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Pertussis Toxin
Cholinergic Receptors
Muscarinic Receptors
Gi-Go GTP-Binding Protein alpha Subunits
Dynamins
Arrestin
Heterotrimeric GTP-Binding Proteins
Clathrin
Cell Surface Receptors
Adenosine Diphosphate
Phosphorylation
Kidney

ASJC Scopus subject areas

  • Pharmacology

Cite this

Agonist-dependent delivery of M2 muscarinic acetylcholine receptors to the cell surface after pertussis toxin treatment. / Roseberry, Aaron G.; Bünemann, Moritz; Elavunkal, Jyoti T.; Hosey, M. Marlene.

In: Molecular Pharmacology, Vol. 59, No. 5, 2001, p. 1256-1268.

Research output: Contribution to journalArticle

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