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MBC in Press, published online ahead of print February 21, 2007
Mol. Biol. Cell 10.1091/mbc.E06-07-0618

A more recent version of this article appeared on May 1, 2007
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Submitted on July 24, 2006
Revised on February 1, 2007
Accepted on February 12, 2007

Caveolin 2 Regulates Endocytosis and Trafficking of the M1 Muscarinic Receptor in MDCK Epithelial Cells

Miriam Shmuel,* Efrat Nodel-Berner,* Tehila Hyman, Alexander Rouvinski, and Yoram Altschuler

Department of Pharmacology, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel

Monitoring Editor: Keith Mostov

Clathrin and caveolins are known for their involvement in the internalization of numerous receptors. Here we show that in polarized epithelial MDCK cells, both the clathrin machinery and caveolins are involved in the endocytosis and delivery to the plasma membrane (PM) of the M1 muscarinic acetylcholine receptor (mAChR). We initially localized this receptor to the lateral membrane, where it accumulates proximal to the tight junctions. From there it is internalized through the clathrin-mediated pathway. In addition, the receptor may associate on the PM with caveolin (cav) 2 or in intracellular compartments with either cav 2, or monomeric or oligomeric cav 1. Association of the PM M1 mAChR with cav 2 inhibits receptor endocytosis through the clathrin-mediated pathway, or retains the receptor in an intracellular compartment. This intracellular association attenuates receptor trafficking. Expression of cav 1 with cav 2 rescues the latter’s inhibitory effect. The caveolins stimulate M1 mAChR oligomerization thus maintaining a constant amount of monomeric receptor. These results provide evidence that caveolins play a role in the attenuation of the M1 muscarinic receptor’s intracellular trafficking to and from the PM.


*These authors contributed equally to this work.

Address correspondence to: Yoram Altschuler (yoram11{at}md.huji.ac.il)







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