β-Catenin, together with LEF1/TCF transcription factors, activates genes involved in the proliferation and differentiation of neuronal precursor cells. In mature neurons, β-catenin participates in dendritogenesis and synaptic function as a component of the cadherin cell adhesion complex. However, the transcriptional activity of β-catenin in these cells remains elusive. In the present study, we found that in the adult mouse brain, β-catenin and LEF1 accumulate in the nuclei of neurons specifically in the thalamus. The particular electrophysiological properties of thalamic neurons depend on T-type calcium channels. Cav3.1 is the predominant T-type channel subunit in the thalamus, and we hypothesized that theCacna1ggene encoding Cav3.1 is a target of the LEF1/β-catenin complex. We demonstrated that the expression ofCacna1gis high in the thalamus and is further increased in thalamic neurons treatedin vitrowith LiCl or WNT3A, activators of β-catenin. Luciferase reporter assays confirmed that theCacna1Gpromoter is activated by LEF1 and β-catenin, and footprinting analysis revealed four LEF1 binding sites in the proximal region of this promoter. Chromatin immunoprecipitation demonstrated that theCacna1gproximal promoter is occupied by β-cateninin vivoin the thalamus, but not in the hippocampus. Moreover, WNT3A stimulation enhanced T-type current in cultured thalamic neurons. Together, our data indicate that the LEF1/β-catenin complex regulates transcription ofCacna1gand uncover a novel function for β-catenin in mature neurons. We propose that β-catenin contributes to neuronal excitability not only by a local action at the synapse but also by activating gene expression in thalamic neurons.

The S100A6 protein is present in different mammalian cells and tissues including the brain. It binds Ca²⁺ and Zn²⁺ and interacts with many target proteins/ligands. The best characterized ligands of S100A6, expressed at high level in the brain, include CacyBP/SIP and Sgt1. Research concerning the functional role of S100A6 and these two ligands indicates that they are involved in various signaling pathways that regulate cell proliferation, differentiation, cytoskeletal organization, and others. In this review, we focused on the expression/localization of these proteins in the brain and on their possible role in neurodegenerative diseases. Published results demonstrate that S100A6, CacyBP/SIP, and Sgt1 are expressed in various brain structures and in the spinal cord and can be found in different cell types including neurons and astrocytes. When it comes to their possible involvement in nervous system pathology, it is evident that their expression/level and/or subcellular localization is changed when compared to normal conditions. Among diseases in which such changes have been observed are Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), epileptogenesis, Parkinson’s disease (PD), Huntington’s disease (HD), and others.