Internalization of the Hm1 muscarinic cholinergic receptor involves the third cytoplasmic loop.
The m1 muscarinic receptor was previously shown to stimulate phosphatidyl inositol (PI) turnover and to internalize rapidly upon agonist activation. Three receptor mutants with large deletions of the third cytoplasmic loop (i3) of human Hm1, leaving only 11 and 8 amino acids at the amino and carboxy terminal junctions of i3, respectively, retained full ability to stimulate PI turnover, when expressed in U293 cells, but receptor internalization was greatly reduced in two mutants with deletions reaching close to the NH2 terminal of i3. We propose that a receptor domain located toward the amino terminal junction of i3 plays a role in Hm1 internalization.
School of Pharmacy, University of California, San Francisco 94143.
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S
Maeda
J
J
Lameh
W G
WG
Mallet
M
M
Philip
J
J
Ramachandran
W
W
Sadée
D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D002872:Chromosome Deletion; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors; D015698:Genomic Library; D006801:Humans; D009154:Mutation; D010716:Phosphatidylinositols / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D002217:Carbachol