Structural highlights
Function
[SYGP1_RAT] Major constituent of the PSD essential for postsynaptic signaling. Inhibitory regulator of the Ras-cAMP pathway. Member of the NMDAR signaling complex in excitatory synapses, it may play a role in NMDAR-dependent control of AMPAR potentiation, AMPAR membrane trafficking and synaptic plasticity. Regulates AMPAR-mediated miniature excitatory postsynaptic currents. May be involved in certain forms of brain injury, leading to long-term learning and memory deficits.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The brain-specific synaptic guanosine triphosphatase (GTPase)-activating protein (SynGAP) is important in synaptic plasticity. It shows dual specificity for the small guanine nucleotide-binding proteins Rap and Ras. Here, we show that RapGAP activity of SynGAP requires its C2 domain. In contrast to the isolated GAP domain, which does not show any detectable RapGAP activity, a fragment comprising the C2 and GAP domains (C2-GAP) stimulates the intrinsic GTPase reaction of Rap by approximately 1 x 10(4). The C2-GAP crystal structure, complemented by modelling and biochemical analyses, favours a concerted movement of the C2 domain towards the switch II region of Rap to assist in GTPase stimulation. Our data support a catalytic mechanism similar to that of canonical RasGAPs and distinct from the canonical RapGAPs. SynGAP presents the first example, to our knowledge, of a GAP that uses a second domain for catalytic activity, thus pointing to a new function of C2 domains.
The C2 domain of SynGAP is essential for stimulation of the Rap GTPase reaction.,Pena V, Hothorn M, Eberth A, Kaschau N, Parret A, Gremer L, Bonneau F, Ahmadian MR, Scheffzek K EMBO Rep. 2008 Apr;9(4):350-5. Epub 2008 Mar 7. PMID:18323856[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Krapivinsky G, Medina I, Krapivinsky L, Gapon S, Clapham DE. SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity and NMDA receptor-dependent synaptic AMPA receptor potentiation. Neuron. 2004 Aug 19;43(4):563-74. PMID:15312654 doi:10.1016/j.neuron.2004.08.003
- ↑ Yang SN, Huang CB, Yang CH, Lai MC, Chen WF, Wang CL, Wu CL, Huang LT. Impaired SynGAP expression and long-term spatial learning and memory in hippocampal CA1 area from rats previously exposed to perinatal hypoxia-induced insults: beneficial effects of A68930. Neurosci Lett. 2004 Nov 16;371(1):73-8. PMID:15500970 doi:http://dx.doi.org/S0304-3940(04)01054-7
- ↑ Rumbaugh G, Adams JP, Kim JH, Huganir RL. SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons. Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4344-51. Epub 2006 Mar 14. PMID:16537406 doi:http://dx.doi.org/0600084103
- ↑ Pena V, Hothorn M, Eberth A, Kaschau N, Parret A, Gremer L, Bonneau F, Ahmadian MR, Scheffzek K. The C2 domain of SynGAP is essential for stimulation of the Rap GTPase reaction. EMBO Rep. 2008 Apr;9(4):350-5. Epub 2008 Mar 7. PMID:18323856 doi:10.1038/embor.2008.20
