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J. Biol. Chem. 286 (36): 31781-31788

© 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

WNT Protein-independent Constitutive Nuclear Localization of β-Catenin Protein and Its Low Degradation Rate in Thalamic Neurons*Formula

Katarzyna Misztal{ddagger}, Marta B. Wisniewska{ddagger}, Mateusz Ambrozkiewicz{ddagger}, Andrzej Nagalski{ddagger}, , and Jacek Kuznicki{ddagger}§1

From the {ddagger}Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, 4 Ks. Trojdena Street, 02-109 Warsaw, Poland and
the §Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, 3 Pasteur Street, 02-093 Warsaw, Poland

ABSTRACT Back to Top

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 Cav3.1 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.


Key Words: β-Catenin • Brain • Neurobiology • Protein Stability • Wnt Pathway • APC-AXIN-GSK3β Degradation Complex • Thalamus

Received for publication February 11, 2011. Revision received July 8, 2011.

1 To whom correspondence should be addressed. Tel.: 48-225970700; Fax: 48-225970715; E-mail: jacek.kuznicki{at}iimcb.gov.pl.



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