Agonist-dependent delivery of M(2) muscarinic acetylcholine receptors
to the cell surface after pertussis toxin treatment
A. Roseberry, M. Bunemann, J. Elavunkal, and M. Hosey. Mol Pharmacol, 59 (5):
1256-68(May 2001)Roseberry, A G Bunemann, M Elavunkal, J Hosey, M M HL50121/HL/NHLBI
NIH HHS/United States T32-GM08061/GM/NIGMS NIH HHS/United States
Research Support, U.S. Gov't, P.H.S. United States Molecular pharmacology
Mol Pharmacol. 2001 May;59(5):1256-68..
Abstract
The internalization of the M(2) 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 M(2) mAChR
was modulated by activation of heterotrimeric G proteins, because
treatment with pertussis toxin, which ADP-ribosylates G proteins
of the G(i/o) family, caused a significant delay in the onset of
internalization of the M(2) mAChR. The effects of pertussis toxin
could not be explained by alteration of the agonist-dependent phosphorylation
of the M(2) 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 M(2) 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.
Roseberry, A G Bunemann, M Elavunkal, J Hosey, M M HL50121/HL/NHLBI
NIH HHS/United States T32-GM08061/GM/NIGMS NIH HHS/United States
Research Support, U.S. Gov't, P.H.S. United States Molecular pharmacology
Mol Pharmacol. 2001 May;59(5):1256-68.
%0 Journal Article
%1 Roseberry2001
%A Roseberry, A. G.
%A Bunemann, M.
%A Elavunkal, J.
%A Hosey, M. M.
%D 2001
%J Mol Pharmacol
%K *Pertussis A/pharmacology Agonists/*pharmacology Apparatus/metabolism Biological Bordetella/*pharmacology Brefeldin Cell Cultured Drug Factors, GTP-Binding Gi-Go/metabolism Golgi Heterotrimeric Humans Inhibitors/pharmacology Interactions M2 Muscarinic Muscarinic/*metabolism Phosphorylation/drug Protein Proteins/metabolism Subunits, Surface/metabolism Synthesis Toxin Transport/drug Virulence alpha effects Receptor
%N 5
%P 1256-68
%T Agonist-dependent delivery of M(2) muscarinic acetylcholine receptors
to the cell surface after pertussis toxin treatment
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11306711
%V 59
%X The internalization of the M(2) 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 M(2) mAChR
was modulated by activation of heterotrimeric G proteins, because
treatment with pertussis toxin, which ADP-ribosylates G proteins
of the G(i/o) family, caused a significant delay in the onset of
internalization of the M(2) mAChR. The effects of pertussis toxin
could not be explained by alteration of the agonist-dependent phosphorylation
of the M(2) 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 M(2) 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.
@article{Roseberry2001,
abstract = {The internalization of the M(2) 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 M(2) mAChR
was modulated by activation of heterotrimeric G proteins, because
treatment with pertussis toxin, which ADP-ribosylates G proteins
of the G(i/o) family, caused a significant delay in the onset of
internalization of the M(2) mAChR. The effects of pertussis toxin
could not be explained by alteration of the agonist-dependent phosphorylation
of the M(2) 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 M(2) 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.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Roseberry, A. G. and Bunemann, M. and Elavunkal, J. and Hosey, M. M.},
biburl = {https://www.bibsonomy.org/bibtex/227d5d65748bbe411574307abbfb177b2/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {7852d2cc546279f55c0d21e7bc985420},
intrahash = {27d5d65748bbe411574307abbfb177b2},
issn = {0026-895X (Print) 0026-895X (Linking)},
journal = {Mol Pharmacol},
keywords = {*Pertussis A/pharmacology Agonists/*pharmacology Apparatus/metabolism Biological Bordetella/*pharmacology Brefeldin Cell Cultured Drug Factors, GTP-Binding Gi-Go/metabolism Golgi Heterotrimeric Humans Inhibitors/pharmacology Interactions M2 Muscarinic Muscarinic/*metabolism Phosphorylation/drug Protein Proteins/metabolism Subunits, Surface/metabolism Synthesis Toxin Transport/drug Virulence alpha effects Receptor},
month = May,
note = {Roseberry, A G Bunemann, M Elavunkal, J Hosey, M M HL50121/HL/NHLBI
NIH HHS/United States T32-GM08061/GM/NIGMS NIH HHS/United States
Research Support, U.S. Gov't, P.H.S. United States Molecular pharmacology
Mol Pharmacol. 2001 May;59(5):1256-68.},
number = 5,
pages = {1256-68},
shorttitle = {Agonist-dependent delivery of M(2) muscarinic acetylcholine receptors
to the cell surface after pertussis toxin treatment},
timestamp = {2010-12-14T18:20:50.000+0100},
title = {Agonist-dependent delivery of M(2) muscarinic acetylcholine receptors
to the cell surface after pertussis toxin treatment},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11306711},
volume = 59,
year = 2001
}