Send to:

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 1994 Jun 3;269(22):15640-5.

Differential role of the carboxyl-terminal tyrosine in down-regulation and sequestration of the m2 muscarinic acetylcholine receptor.

Author information

  • 1Department of Pharmacology, University of Washington, Seattle 98195.


Muscarinic acetylcholine receptor (mAChR) number can be altered in response to sustained agonist exposure. Short term agonist exposure (seconds to minutes) causes a rapid removal of mAChR from the cell surface (sequestration) while agonist exposure for longer periods of time (hours) causes a decrease in total receptor number (down-regulation). Tyrosine residues located in the cytoplasmic tails of a number of membrane receptors have been demonstrated to be important in the regulation by either sequestration, as is the case with the mannose 6-phosphate receptor and other receptors endocytosed via clathrin coated vesicles, or down-regulation, as is the case with the beta 2-adrenergic receptor. Mutation of the lone cytoplasmic tail tyrosine residue (Tyr-459) of the mammalian m2 mAChR to Phe, Trp, or Ala did not affect agonist-induced sequestration, although it significantly attenuated agonist-induced down-regulation. Conversion of m2 Tyr-459 to Ile did not affect the rate or extent of agonist-induced sequestration or down-regulation, but the sensitivity of this mutant receptor to agonist-induced down-regulation was slightly decreased. Agonist and antagonist binding as well as functional coupling to the inhibition of cAMP accumulation was unaffected by any of the mutations to Tyr-459. These results are the first to identify a site in a mAChR involved in the down-regulation of receptor in response to agonist.

[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk