PSD-95 (postsynaptic density-95) is thought to play important roles in the regulation of dendritic spines and excitatory synapses, but the underlying mechanisms have not been fully elucidated. TANC1 is a PSD-95-interacting synaptic protein that contains multiple domains for protein-protein interactions but whose function is not well understood. In the present study, we provide evidence that TANC1 and its close relative TANC2 regulate dendritic spines and excitatory synapses. Overexpression of TANC1 and TANC2 in cultured neurons increases the density of dendritic spines and excitatory synapses in a manner that requires the PDZ (PSD-95/Dlg/ZO-1)-binding C termini of TANC proteins. TANC1-deficient mice exhibit reduced spine density in the CA3 region of the hippocampus, but not in the CA1 or dentate gyrus regions, and show impaired spatial memory. TANC2 deficiency, however, causes embryonic lethality. These results suggest that TANC1 is important for dendritic spine maintenance and spatial memory, and implicate TANC2 in embryonic development.
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