Skip to Content
Merck
  • Alteration by p11 of mGluR5 localization regulates depression-like behaviors.

Alteration by p11 of mGluR5 localization regulates depression-like behaviors.

Molecular psychiatry (2015-09-16)
K-W Lee, L Westin, J Kim, J C Chang, Y-S Oh, B Amreen, J Gresack, M Flajolet, D Kim, A Aperia, Y Kim, P Greengard
ABSTRACT

Mood disorders and antidepressant therapy involve alterations of monoaminergic and glutamatergic transmission. The protein S100A10 (p11) was identified as a regulator of serotonin receptors, and it has been implicated in the etiology of depression and in mediating the antidepressant actions of selective serotonin reuptake inhibitors. Here we report that p11 can also regulate depression-like behaviors via regulation of a glutamatergic receptor in mice. p11 directly binds to the cytoplasmic tail of metabotropic glutamate receptor 5 (mGluR5). p11 and mGluR5 mutually facilitate their accumulation at the plasma membrane, and p11 increases cell surface availability of the receptor. Whereas p11 overexpression potentiates mGluR5 agonist-induced calcium responses, overexpression of mGluR5 mutant, which does not interact with p11, diminishes the calcium responses in cultured cells. Knockout of mGluR5 or p11 specifically in glutamatergic neurons in mice causes depression-like behaviors. Conversely, knockout of mGluR5 or p11 in GABAergic neurons causes antidepressant-like behaviors. Inhibition of mGluR5 with an antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), induces antidepressant-like behaviors in a p11-dependent manner. Notably, the antidepressant-like action of MPEP is mediated by parvalbumin-positive GABAergic interneurons, resulting in a decrease of inhibitory neuronal firing with a resultant increase of excitatory neuronal firing. These results identify a molecular and cellular basis by which mGluR5 antagonism achieves its antidepressant-like activity.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
D-Glucose-12C6, 16O6, 99.9 atom % 16O, 99.9 atom % 12C
Sigma-Aldrich
Sodium bicarbonate, powder, BioReagent, for molecular biology, suitable for cell culture, suitable for insect cell culture
Sigma-Aldrich
HEPES, ≥99.5% (titration)
Sigma-Aldrich
D-(+)-Glucose, ≥99.5% (GC), BioXtra
Sigma-Aldrich
HEPES, BioPerformance Certified, ≥99.5% (titration), suitable for cell culture
Sigma-Aldrich
D-(+)-Glucose, ACS reagent
Sigma-Aldrich
D-(+)-Glucose, ≥99.5% (GC)
Sigma-Aldrich
D-(+)-Glucose, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99.5%
Sigma-Aldrich
D-(+)-Glucose, BioUltra, anhydrous, ≥99.5% (sum of enantiomers, HPLC)
Sigma-Aldrich
Sodium bicarbonate, ACS reagent, ≥99.7%
Sigma-Aldrich
Sodium bicarbonate-12C, 99.9 atom % 12C
Sigma-Aldrich
HEPES buffer solution, 1 M in H2O
Sigma-Aldrich
Dextrose, 97.5-102.0% anhydrous basis, meets EP, BP, JP, USP testing specifications
Sigma-Aldrich
Anti-Glyceraldehyde-3-Phosphate Dehydrogenase Antibody, clone 6C5, clone 6C5, Chemicon®, from mouse