RGD Reference Report - Subunit-selective N-Methyl-d-aspartate (NMDA) Receptor Signaling through Brefeldin A-resistant Arf Guanine Nucleotide Exchange Factors BRAG1 and BRAG2 during Synapse Maturation. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Subunit-selective N-Methyl-d-aspartate (NMDA) Receptor Signaling through Brefeldin A-resistant Arf Guanine Nucleotide Exchange Factors BRAG1 and BRAG2 during Synapse Maturation.

Authors: Elagabani, MN  Brisevac, D  Kintscher, M  Pohle, J  Kohr, G  Schmitz, D  Kornau, HC 
Citation: Elagabani MN, etal., J Biol Chem. 2016 Apr 22;291(17):9105-18. doi: 10.1074/jbc.M115.691717. Epub 2016 Feb 16.
RGD ID: 11560558
Pubmed: PMID:26884337   (View Abstract at PubMed)
PMCID: PMC4861478   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M115.691717   (Journal Full-text)

The maturation of glutamatergic synapses in the CNS is regulated by NMDA receptors (NMDARs) that gradually change from a GluN2B- to a GluN2A-dominated subunit composition during postnatal development. Here we show that NMDARs control the activity of the small GTPase ADP-ribosylation factor 6 (Arf6) by consecutively recruiting two related brefeldin A-resistant Arf guanine nucleotide exchange factors, BRAG1 and BRAG2, in a GluN2 subunit-dependent manner. In young cortical cultures, GluN2B and BRAG1 tonically activated Arf6. In mature cultures, Arf6 was activated through GluN2A and BRAG2 upon NMDA treatment, whereas the tonic Arf6 activation was not detectable any longer. This shift in Arf6 regulation and the associated drop in Arf6 activity were reversed by a knockdown of BRAG2. Given their sequential recruitment during development, we examined whether BRAG1 and BRAG2 influence synaptic currents in hippocampal CA1 pyramidal neurons using patch clamp recordings in acute slices from mice at different ages. The number of AMPA receptor (AMPAR) miniature events was reduced by depletion of BRAG1 but not by depletion of BRAG2 during the first 2 weeks after birth. In contrast, depletion of BRAG2 during postnatal weeks 4 and 5 reduced the number of AMPAR miniature events and compromised the quantal sizes of both AMPAR and NMDAR currents evoked at Schaffer collateral synapses. We conclude that both Arf6 activation through GluN2B-BRAG1 during early development and the transition from BRAG1- to BRAG2-dependent Arf6 signaling induced by the GluN2 subunit switch are critical for the development of mature glutamatergic synapses.



Gene Ontology Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Grin2a  (glutamate ionotropic receptor NMDA type subunit 2A)
Grin2b  (glutamate ionotropic receptor NMDA type subunit 2B)
Iqsec1  (IQ motif and Sec7 domain ArfGEF 1)
Iqsec2  (IQ motif and Sec7 domain ArfGEF 2)


Additional Information