Characterization of in vivo functions of the postsynaptic scaffolding protein TANC2

Abstract

PSD-95 (postsynaptic density-95) is a major scaffolding protein of the excitatory postsynaptic density and has a significant influence on the regulation of dendritic spines and excitatory synapses. TANC2 (Tetratrico-peptide Repeat, Ankyrin Repeat and Coiled-Coil Containing 2) is a novel binding partner of PSD-95 and is expressed widely in the various brain regions. It was originally reported that TANC2 has positive influences on dendritic spines and excitatory synapses and also implication in embryonic development. However, in vivo functions of TANC2 still remain obscure, and TANC2 knockout mice is embryonic lethal. Here, using TANC2 hetero ($TANC2^{+/-}$) mice, I demonstrate that the mutant mice show enhanced basal inhibitory synaptic transmission whereas basal excitatory synaptic transmission is reduced in the hippocampal dentate gyrus. Behaviorally, $TANC2^{+/-}$ mice show hyperactivity in a novel environment and impaired contextual fear conditioning, but normal levels of object recognition memory. These results suggest that TANC2 may be an important regulator of synaptic plasticity and altered behaviors