| First Author | Scholz R | Year | 2010 |
| Journal | Neuron | Volume | 66 |
| Issue | 5 | Pages | 768-80 |
| PubMed ID | 20547133 | Mgi Jnum | J:163183 |
| Mgi Id | MGI:4821212 | Doi | 10.1016/j.neuron.2010.05.003 |
| Citation | Scholz R, et al. (2010) AMPA receptor signaling through BRAG2 and Arf6 critical for long-term synaptic depression. Neuron 66(5):768-80 |
| abstractText | Central nervous system synapses undergo activity-dependent alterations to support learning and memory. Long-term depression (LTD) reflects a sustained reduction of the synaptic AMPA receptor content based on targeted clathrin-mediated endocytosis. Here we report a current-independent form of AMPA receptor signaling, fundamental for LTD. We found that AMPA receptors directly interact via the GluA2 subunit with the synaptic protein BRAG2, which functions as a guanine-nucleotide exchange factor (GEF) for the coat-recruitment GTPase Arf6. BRAG2-mediated catalysis, controlled by ligand-binding and tyrosine phosphorylation of GluA2, activates Arf6 to internalize synaptic AMPA receptors upon LTD induction. Furthermore, acute blockade of the GluA2-BRAG2 interaction and targeted deletion of BRAG2 in mature hippocampal CA1 pyramidal neurons prevents LTD in CA3-to-CA1 cell synapses, irrespective of the induction pathway. We conclude that BRAG2-mediated Arf6 activation triggered by AMPA receptors is the convergent step of different forms of LTD, thus providing an essential mechanism for the control of vesicle formation by endocytic cargo. |
