Drosophila Naked cuticle (Nkd) engages the nuclear import adaptor Importin-alpha3 to antagonize Wnt/beta-catenin signaling.

Developmental Biology
Chih-Chiang ChanKeith A Wharton

Abstract

Precise control of Wnt/beta-catenin signaling is critical for animal development, stem cell renewal, and prevention of disease. In the fruit fly Drosophila melanogaster, the naked cuticle (nkd) gene limits signaling by the Wnt ligand Wingless (Wg) during embryo segmentation. Nkd is an intracellular protein that is composed of separable membrane- and nuclear-localization sequences (NLS) as well as a conserved EF-hand motif that binds the Wnt receptor-associated scaffold protein Dishevelled (Dsh), but the mechanism by which Nkd inhibits Wnt signaling remains a mystery. Here we identify a second NLS in Nkd that is required for full activity and that binds to the canonical nuclear import adaptor Importin-alpha3. The Nkd NLS is similar to the Importin-alpha3-binding NLS in the Drosophila heat-shock transcription factor (dHSF), and each Importin-alpha3-binding NLS required intact basic residues in similar positions for nuclear import and protein function. Our results provide further support for the hypothesis that Nkd inhibits nuclear step(s) in Wnt/beta-catenin signaling and broaden our understanding of signaling pathways that engage the nuclear import machinery.

References

Aug 1, 1995·Developmental Biology·K B YoffeN Perrimon
May 1, 1995·Genes & Development·S YanagawaR Nusse
Jan 1, 1995·Annual Review of Cell and Developmental Biology·C Wu
May 24, 2000·Proceedings of the National Academy of Sciences of the United States of America·J C ClemensJ E Dixon
Mar 29, 2001·Genes & Development·R RoussetM P Scott
Oct 18, 2001·International Journal of Oncology·M Katoh
Dec 26, 2001·Current Opinion in Structural Biology·Y M Chook, G Blobel
Oct 2, 2002·The Journal of Biological Chemistry·Raphaël RoussetMatthew P Scott
Dec 18, 2002·The Journal of Biological Chemistry·Michelle T HarremanAnita H Corbett
Nov 25, 2003·The Journal of Biological Chemistry·Nicola WiechensFrançois Fagotto
Feb 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Feng Cong, Harold Varmus
Sep 8, 2004·Trends in Cell Biology·David S GoldfarbStephen A Adam
Feb 22, 2005·Journal of Biology·Keiji ItohSergei Y Sokol
Jun 6, 2006·Genes & Development·Karl Willert, Katherine A Jones
Sep 22, 2006·Developmental Biology·Lei ZhangJin Jiang
Dec 16, 2006·The Journal of Biological Chemistry·Allison LangeAnita H Corbett
Jun 26, 2007·FEBS Letters·Ruiwen Wang, Michael G Brattain
Aug 11, 2007·Developmental Biology·Terence J Van RaayLilianna Solnica-Krezel
Sep 21, 2007·Journal of Cell Science·Koji Aoki, Makoto M Taketo
Sep 1, 1984·Wilhelm Roux's Archives of Developmental Biology·G JürgensH Kluding

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Citations

Apr 16, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Misao E Higashi-KovtunThomas L Schwarz
Dec 15, 2010·PloS One·Timothy J Mosca, Thomas L Schwarz
Apr 15, 2011·PloS One·Terence J Van RaayRobert J Coffey
Apr 24, 2015·Molecular Biology of the Cell·Jahdiel LarraguibelTerence J Van Raay
Oct 23, 2009·International Journal of Cancer. Journal International Du Cancer·Silke GötzeSonja Sievers
Oct 15, 2014·Developmental Neurobiology·Tasha JoyChris Q Doe
Feb 24, 2011·European Journal of Haematology·Alexandra FilipovichKarl-Anton Kreuzer
May 30, 2019·BioMed Research International·Jinqian LiangJianhua Hu
Sep 3, 2021·Biochemical and Biophysical Research Communications·Rui WangMing Fang
Jun 11, 2009·Seminars in Cell & Developmental Biology·D Adam Mason, David S Goldfarb

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