Editors' ChoiceCell Biology

A Wnt-Less Journey to the Nucleus?

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Science Signaling  13 Sep 2011:
Vol. 4, Issue 190, pp. ec254
DOI: 10.1126/scisignal.4190ec254

Activation of the canonical Wnt signaling pathway, which is critical to brain development, decreases the proteasomal degradation of cytoplasmic β-catenin, allowing β-catenin to translocate to the nucleus to activate Wnt target genes. Noting that, atypically, β-catenin is found in the nuclei of mature thalamic neurons in the adult brain, Misztal et al. cultured neurons from embryonic day 19 rat brain and determined that, after 7 days in vitro, thalamic neurons, unlike cortical or hippocampal neurons, showed nuclear accumulation of β-catenin. Nuclear localization of β-catenin in cultured thalamic neurons was independent of survival-promoting factors in conditioned medium from cortical cultures and was unaffected by treatment with arabinofuranosylcytosine (AraC), which markedly reduced the number of glia in the cultures. Moreover, conditioned medium from the thalamic cultures failed to activate Wnt signaling in HEK 293 cells transfected with a Wnt-responsive reporter, and treatment with Wnt antagonists (Dickkopf1 or a dominant negative form of Dishevelled 3) failed to decrease nuclear accumulation of β-catenin in thalamic neurons. Cytoplasmic β-catenin is marked for degradation by a complex containing axin, adenomatous polyposis coli (APC) protein, and glycogen synthase kinase 3 (GSK-3), and immunoblot analysis revealed that the abundance of axin1, APC, and GSK-3β was lower in the thalamus of adult rats than in the cortex. Similarly, the abundance of these three proteins was lower in thalamic than cortical neuronal cultures (grown in the presence of AraC). Analysis of the stability of radioactively labeled β-catenin indicated that degradation of cytoplasmic β-catenin occurred more slowly in thalamic than cortical neuronal cultures. The authors thus propose that nuclear accumulation of β-catenin in thalamic neurons represents a cell-intrinsic property that is independent of Wnt signaling and associated with low abundance of components of the axin-APC-GSK-3 destruction complex.

K. Misztal, M. B. Wisniewska, M. Ambrozkiewicz, A. Nagalski, J. Kuznicki, WNT protein-independent constitutive nuclear localization of β-catenin protein and its low degradation rate in thalamic neurons. J. Biol. Chem. 286, 31781–31788 (2011). [Abstract] [Full Text]

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