Metabotropic glutamate receptor internalization and synaptic AMPA receptor endocytosis by dopamine
- 1Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, Knowledge city, Sector – 81, SAS Nagar, 140306, Punjab, India
Abstract
Group I metabotropic glutamate receptors (mGluRs) play important roles in synaptic function and plasticity, and in many neuropsychiatric disorders. Trafficking plays crucial roles in proper targeting of these receptors in specific regions of the neuron and in regulating the activity of these receptors. Group I mGluRs encounter dopamine in various regions of the brain and multiple findings suggest that dopamine regulates these receptors in the hippocampus. We show here that dopamine induces internalization of both members of the group I mGluR family, mGluR1 (also known as GRM1) and mGluR5 (GRM5), in hippocampal neurons derived from mice through a clathrin-dependent but dynamin-independent pathway. Dopamine increases mGluR-mediated Gαq (also known as GNAQ) activity and phosphorylation of MAP kinases. Following dopamine-mediated internalization, receptors recycle to the cell surface faster than the recycling of agonist-mediated internalized receptors. Recycling of the dopamine-mediated internalized mGluR1 is protein phosphatase 2B dependent. Finally, we report that dopamine also induces mGluR-mediated synaptic AMPA receptor endocytosis, the cellular correlate of mGluR-dependent synaptic plasticity. Thus, this study unravels a novel role for dopamine in the internalization of mGluRs and mGluR-mediated AMPA receptor endocytosis.
Related
- Seizures and tauopathy following neurotrauma are mediated by prion protein and metabotropic glutamate receptor 5
- Novel Co-expression of Group I Metabotropic Glutamate Receptor During Mouse Cochlear Nucleus Development
- Photocontrol of Metabotropic Glutamate Receptors: When One Agonist Is Not Enough, Make It Two
- Postmortem Alterations of Metabotropic Glutamate Receptors across Neuropsychiatric Disorders: A Systematic Review
- Anti-HER2 immunotoxin scFv-PE35KDEL internalizes via receptor-mediated endocytosis and induces apoptosis in ovarian cancer cells
BibTeX
@article{aruna2026metabotropic,
title = {{Metabotropic glutamate receptor internalization and synaptic AMPA receptor endocytosis by dopamine}},
author = {K Aruna and Mitra Kulkarni and Samarjit Bhattacharyya},
journal = {Journal of Cell Science},
year = {2026},
month = aug,
doi = {10.1242/jcs.264725},
url = {https://doi.org/10.1242/jcs.264725},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Metabotropic glutamate receptor internalization and synaptic AMPA receptor endocytosis by dopamine
AU - K Aruna
AU - Mitra Kulkarni
AU - Samarjit Bhattacharyya
PY - 2026
DA - 2026/08/13
JO - Journal of Cell Science
DO - 10.1242/jcs.264725
UR - https://doi.org/10.1242/jcs.264725
AB - Group I metabotropic glutamate receptors (mGluRs) play important roles in synaptic function and plasticity, and in many neuropsychiatric disorders. Trafficking plays crucial roles in proper targeting of these receptors in specific regions of the neuron and in regulating the activity of these receptors. Group I mGluRs encounter dopamine in various regions of the brain and multiple findings suggest that dopamine regulates these receptors in the hippocampus. We show here that dopamine induces internalization of both members of the group I mGluR family, mGluR1 (also known as GRM1) and mGluR5 (GRM5), in hippocampal neurons derived from mice through a clathrin-dependent but dynamin-independent pathway. Dopamine increases mGluR-mediated Gαq (also known as GNAQ) activity and phosphorylation of MAP kinases. Following dopamine-mediated internalization, receptors recycle to the cell surface faster than the recycling of agonist-mediated internalized receptors. Recycling of the dopamine-mediated internalized mGluR1 is protein phosphatase 2B dependent. Finally, we report that dopamine also induces mGluR-mediated synaptic AMPA receptor endocytosis, the cellular correlate of mGluR-dependent synaptic plasticity. Thus, this study unravels a novel role for dopamine in the internalization of mGluRs and mGluR-mediated AMPA receptor endocytosis.
SN - 0021-9533
SN - 1477-9137
ER -