TY - JOUR
T1 - Endosomal Wnt signaling proteins control microtubule nucleation in dendrites
AU - Weiner, Alexis T.
AU - Seebold, Dylan Y.
AU - Torres-Gutierrez, Pedro
AU - Folker, Christin
AU - Swope, Rachel D.
AU - Kothe, Gregory O.
AU - Stoltz, Jessica G.
AU - Zalenski, Madeleine K.
AU - Kozlowski, Christopher
AU - Barbera, Dylan J.
AU - Patel, Mit A.
AU - Thyagarajan, Pankajam
AU - Shorey, Matthew
AU - Nye, Derek M.R.
AU - Keegan, Matthew
AU - Behari, Kana
AU - Song, Song
AU - Axelrod, Jeffrey D.
AU - Rolls, Melissa M.
N1 - Publisher Copyright:
Copyright: © 2020 Weiner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2020/3
Y1 - 2020/3
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85081937087
UR - https://www.scopus.com/pages/publications/85081937087#tab=citedBy
U2 - 10.1371/journal.pbio.3000647
DO - 10.1371/journal.pbio.3000647
M3 - Article
C2 - 32163403
AN - SCOPUS:85081937087
SN - 1544-9173
VL - 18
JO - PLoS biology
JF - PLoS biology
IS - 3
M1 - e3000647
ER -