title: WNT protein-independent constitutive nuclear localization of beta-catenin protein and its low degradation rate in thalamic neurons.
abstract: Nuclear localization of β-catenin is a hallmark of canonical Wnt signaling, a pathway that plays a crucial role in brain development and the neurogenesis of the adult brain. We recently showed that β-catenin accumulates specifically in mature thalamic neurons, where it regulates the expression of the Ca(v)3.1 voltage-gated calcium channel gene. Here, we investigated the mechanisms underlying β-catenin accumulation in thalamic neurons. We report that a lack of soluble factors produced either by glia or cortical neurons does not impair nuclear β-catenin accumulation in thalamic neurons. We next found that the number of thalamic neurons with β-catenin nuclear localization did not change when the Wnt/Dishevelled signaling pathway was inhibited by Dickkopf1 or a dominant negative mutant of Dishevelled3. These results suggest a WNT-independent cell-autonomous mechanism. We found that the protein levels of APC, AXIN1, and GSK3β, components of the β-catenin degradation complex, were lower in the thalamus than in the cortex of the adult rat brain. Reduced levels of these proteins were also observed in cultured thalamic neurons compared with cortical cultures. Finally, pulse-chase experiments confirmed that cytoplasmic β-catenin turnover was slower in thalamic neurons than in cortical neurons. Altogether, our data indicate that the nuclear localization of β-catenin in thalamic neurons is their cell-intrinsic feature, which was WNT-independent but associated with low levels of proteins involved in β-catenin labeling for ubiquitination and subsequent degradation.
authors.affiliation: Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, 4 Ks. Trojdena Street, 02-109 Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Misztal
authors.forename: Marta B
authors.initials: MB
authors.lastname: Wisniewska
authors.forename: Mateusz
authors.initials: M
authors.lastname: Ambrozkiewicz
authors.forename: Andrzej
authors.initials: A
authors.lastname: Nagalski
authors.forename: Jacek
authors.initials: J
authors.lastname: Kuznicki
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D009474:Neurons / Q000378:metabolism*; D055550:Protein Stability; D051381:Rats; D017208:Rats, Wistar; D013788:Thalamus / Q000166:cytology*; D054875:Ubiquitination; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495268:Ctnnb1 protein, rat; D051153:Wnt Proteins; D051176:beta Catenin