Other
14 Authors
- Yu S,
- Petralia RS,
- Moore CG,
- Park JM,
- Kammermeier PJ,
- Dong X,
- Hu JH,
- Xiao B,
- Zhang PW,
- Yang L,
- Brakeman PR,
- Worley PF,
- Li Z,
- Tu J
| First Author | Hu JH | Year | 2012 |
| Journal | Nat Neurosci | Volume | 15 |
| Issue | 6 | Pages | 836-44 |
| PubMed ID | 22561452 | Mgi Jnum | J:191366 |
| Mgi Id | MGI:5461603 | Doi | 10.1038/nn.3103 |
| Citation | Hu JH, et al. (2012) Preso1 dynamically regulates group I metabotropic glutamate receptors. Nat Neurosci 15(6):836-44 |
| abstractText | Group I metabotropic glutamate receptors (mGluRs), including mGluR1 and mGluR5, are G protein-coupled receptors (GPCRs) that are expressed at excitatory synapses in brain and spinal cord. GPCRs are often negatively regulated by specific G protein-coupled receptor kinases and subsequent binding of arrestin-like molecules. Here we demonstrate an alternative mechanism in which group I mGluRs are negatively regulated by proline-directed kinases that phosphorylate the binding site for the adaptor protein Homer, and thereby enhance mGluR-Homer binding to reduce signaling. This mechanism is dependent on a multidomain scaffolding protein, Preso1, that binds mGluR, Homer and proline-directed kinases and that is required for their phosphorylation of mGluR at the Homer binding site. Genetic ablation of Preso1 prevents dynamic phosphorylation of mGluR5, and Preso1(-/-) mice exhibit sustained, mGluR5-dependent inflammatory pain that is linked to enhanced mGluR signaling. Preso1 creates a microdomain for proline-directed kinases with broad substrate specificity to phosphorylate mGluR and to mediate negative regulation. |
