ArticleScientific reports2015
Unraveling a molecular determinant for clathrin-independent internalization of the M2 muscarinic acetylcholine receptor.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Transcriptional and functional profiles of muscarinic receptor-expressing neurons in primate lateral prefrontal and anterior cingulate cortices.Communications biology · 2026Article
- Activity-dependent muscarinic signalling regulates presynaptic PKC pathway and neurotransmission machinery at the neuromuscular junction.Cell communication and signaling : CCS · 2025Article
- ATP8A1-translocated endosomal phosphatidylserine fine-tunes the multivesicular body formation and the endo-lysosomal traffic.iScience · 2025Article
- A Rab10-ACAP1-Arf6 GTPases cascade modulates M4 muscarinic acetylcholine receptor trafficking and signaling.Cellular and molecular life sciences : CMLS · 2023Article
- Diversity and specificity in location-based signaling outputs of neuronal GPCRs.Current opinion in neurobiology · 2022Review
- The GRKs Reactome: Role in Cell Biology and Pathology.International journal of molecular sciences · 2021Review
- Review
- Molecular characterization of frog vocal neurons using constellation pharmacology.Journal of neurophysiology · 2020Article
- Role of Muscarinic Acetylcholine Receptors in Breast Cancer: Design of Metronomic Chemotherapy.Current clinical pharmacology · 2019Review
- hTAC internalizes via both clathrin-dependent and clathrin-independent endocytosis in mammalian cells.Protein & cell · 2018Article
- Endocytosis of Activated Muscarinic m2 Receptor (m2R) in Live Mouse Hippocampal Neurons Occurs via a Clathrin-Dependent Pathway.Frontiers in cellular neuroscience · 2018Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endocytosis and postendocytic sorting of G-protein-coupled receptors (GPCRs) is important for the regulation of both their cell surface density and signaling profile. Unlike the mechanisms of clathrin-dependent endocytosis (CDE), the mechanisms underlying the control of GPCR signaling by clathrin-independent endocytosis (CIE) remain largely unknown. Among the muscarinic acetylcholine receptors (mAChRs), the M4 mAChR undergoes CDE and recycling, whereas the M2 mAChR is internalized through CIE and targeted to lysosomes. Here we investigated the endocytosis and postendocytic trafficking of M2 mAChR based on a comparative analysis of the third cytoplasmic domain in M2 and M4 mAChRs. For the first time, we identified that the sequence (374)KKKPPPS(380) servers as a sorting signal for the clathrin-independent internalization of M2 mAChR. Switching (374)KKKPPPS(380) to the i3 loop of the M4 mAChR shifted the receptor into lysosomes through the CIE pathway; and therefore away from CDE and recycling. We also found another previously unidentified sequence that guides CDE of the M2 mAChR, (361)VARKIVKMTKQPA(373), which is normally masked in the presence of the downstream sequence (374)KKKPPPS(380). Taken together, our data indicate that endocytosis and postendocytic sorting of GPCRs that undergo CIE could be sequence-dependent.
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