Fig. 1

Schematic of signaling pathways regulated by Syngap1 gene. SynGAP protein has been shown to inhibit the activation of various small GTPases. In dendritic spines, SynGAP suppresses Ras/Erk activity and limits growth-related processes including protein translation and AMPA receptor exocytosis. Reduced SynGAP protein levels causes elevated basal Ras/Erk signaling. This results in increased AMPAR surface incorporation thought to contribute to excessive excitation in neural circuits. Enhanced Ras/ERK signaling is also linked to impaired synaptic plasticity, such as altered hippocampal long-term potentiation. Although Rab5 and Rap GTPases are regulated by SynGAP, these mechanisms are poorly understood and it remains unknown how they contribute to Syngap1-related disorders