Differential role of the carboxyl-terminal tyrosine in down-regulation and sequestration of the m2 muscarinic acetylcholine receptor
| Autor: | P S, Goldman, N M, Nathanson |
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| Rok vydání: | 1994 |
| Předmět: |
Molecular Sequence Data
Scopolamine Derivatives Down-Regulation Transfection Cell Line Pregnancy Cyclic AMP Tumor Cells Cultured Animals Humans Amino Acid Sequence Choriocarcinoma Luciferases Mammals Sequence Homology Amino Acid Cell Membrane N-Methylscopolamine beta-Galactosidase Receptors Muscarinic Quinuclidinyl Benzilate Kinetics Uterine Neoplasms Mutagenesis Site-Directed Tyrosine Carbachol Female Receptors Adrenergic beta-2 |
| Zdroj: | The Journal of biological chemistry. 269(22) |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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