Fig. 2: Schematic description of the role of nArgBP2 in excitatory spine-synapse formation and maintenance of E/I balance.
From: nArgBP2-SAPAP-SHANK, the core postsynaptic triad associated with psychiatric disorders
In the normal condition, nArgBP2 plays a role in controlling actin cytoskeleton dynamics through the WAVE and PAK/cofilin cascade. Its ablation, however, increases actin dynamics via uncontrolled phosphorylation of the WAVE/PAK/cofilin pathway, causing a robust and selective inhibition of excitatory spine-synapse formation. This subsequently leads to an excitatory/inhibitory synaptic imbalance. Since the excitatory/inhibitory synaptic imbalance likely leads to a broad spectrum of psychiatric disorders, nArgBP2 KD, which selectively alters excitatory synapse formation, may account for the manic/bipolar-like behaviors observed in nArgBP2 KO mice
