Paper (Ras)

Grigory Krapivinsky, David E. Clapham (2004) "SynGAP-MUPP1-CaMKII Synaptic Complexes Regulate p38 MAP Kinase Activity and NMDA Receptor- Dependent Synaptic AMPA Receptor Potentiation" Neuron, 43, 563-574
[Note] Calcium dependent activation of Ras and other GTPase proteins are esential for synaptic plasticities. There have been two known calciu-dependent Ras effectors, RasGRF1 and SynGAP. SynGAP is highly abundant in postsynaptic density, and phosphorylated by CaMKII. This paper beautifully have shown the role of SynGAP. First, SynGAP is phosphorylated by CaMKII in normal condition. Direct interactions via MUPP1 is required for this phosphorylation. Upon calcium entry through NMDAR, CaMKII is released from MUPP1, and thus, SynGAP is DEPHOSPHORYLATED. Blocking CAMKII-SynGAP interaction via specific peptides causes decease activity of MAP38, and increases AMPAR at synapses. They also found that SynGAP inactivates Rap1 better than Ras. They hypothesize that SynGAP dephosphorylation activates GAP activity of SynGAP to inhibit Rap1.