SynGAP/A0024

Synaptic Ras GTPase-activating protein 1 (SynGAP), also known as A0024, is a negative regulator of the Ras-cyclic adenosine monophosphate (cAMP) pathway.

Synaptic Ras GTPase-activating protein 1 (SynGAP), also known as A0024, is a negative regulator of the Ras-cyclic adenosine monophosphate (cAMP) pathway. SynGAP is abundant constituent of the post-synaptic density, and essential for post-synaptic signaling. This protein also is expressed within axons and growth cones of developing mouse granule cells. Over-expression of SynGAP blocked neurite outgrowth. SynGAP is a member of the N-methyl-D-aspartate receptor (NMDAR)-signaling complex, it has been involved in NMDAR-dependent control of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) potentiation, AMPAR membrane trafficking and the number of silent synapses, all these mechanics are related to synaptic plasticity. Homozygote mutation of this proteins is lethal, but in heterozygous SynGAP(-/+) mice, the long-term potentiation (LTP) induction in the CA1 region of the hippocampus was strongly reduced, this mice don’t show any detectable alteration in basal synaptic transmission and NMDAR-mediated synaptic currents. Although this mice display a elevated basal levels of activated extracellular signal-regulated kinase 2 (ERK2) and the potentiation induced by stimulation protocols that induce an ERK-independent form of LTP were also significantly reduced in slices from SynGAP(-/+), consequently its role in LTP most likely involves additional downstream targets.