Journal Article

Endosomal Wnt signaling proteins control microtubule nucleation in dendrites

Song, Song, Axelrod, Jeffrey D., Swope, Rachel D., Kothe, Gregory O., Zalenski, Madeleine K., Shorey, Matthew, Kozlowski, Christopher, Patel, Mit A., Behari, Kana, Weiner, Alexis T., Stoltz, Jessica G., Seebold, Dylan Y., Nye, Derek M. R., Thyagarajan, Pankajam, Keegan, Matthew, Rolls, Melissa M., Torres-Gutierrez, Pedro, Folker, Christin, Barbera, Dylan J.

2020

Overview

Dendrite microtubules are polarized with minus-end-out orientation in Drosophila neurons. Nucleation sites concentrate at dendrite branch points, but how they localize is not known. Using Drosophila, we found that canonical Wnt signaling proteins regulate localization of the core nucleation protein γTubulin (γTub). Reduction of frizzleds (fz), arrow (low-density lipoprotein receptor-related protein [LRP] 5/6), dishevelled (dsh), casein kinase Iγ, G proteins, and Axin reduced γTub-green fluorescent protein (GFP) at branch points, and two functional readouts of dendritic nucleation confirmed a role for Wnt signaling proteins. Both dsh and Axin localized to branch points, with dsh upstream of Axin. Moreover, tethering Axin to mitochondria was sufficient to recruit ectopic γTub-GFP and increase microtubule dynamics in dendrites. At dendrite branch points, Axin and dsh colocalized with early endosomal marker Rab5, and new microtubule growth initiated at puncta marked with fz, dsh, Axin, and Rab5. We propose that in dendrites, canonical Wnt signaling proteins are housed on early endosomes and recruit nucleation sites to branch points.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Animals / Axin Signaling Complex - genetics / Axin Signaling Complex - metabolism / Axons - metabolism / Biochemistry / Biology and Life Sciences / Casein / Cell Polarity / Chemical properties / Control / Dendrites / Dendrites - genetics / Dendrites - metabolism / Dendritic structure / Dishevelled protein / Drosophila / Drosophila Proteins - genetics / Drosophila Proteins - metabolism / Endosomes / Endosomes - genetics / Endosomes - metabolism / Fluorescence / Green fluorescent protein / Influence / Insects / Kinases / Localization / Microtubules / Microtubules - genetics / Microtubules - metabolism / Mitochondria / Molecular biology / Mutation / Neurons / Nucleation / Physical Sciences / Proteins / rab5 GTP-Binding Proteins - genetics / rab5 GTP-Binding Proteins - metabolism / Receptor density / Receptors, Wnt - genetics / Receptors, Wnt - metabolism / Signaling / Structure / Tethering / Tubulin - genetics / Tubulin - metabolism / Wnt protein / Wnt proteins / Wnt Proteins - genetics / Wnt Proteins - metabolism / Wnt Signaling Pathway - genetics