Glycolysis regulates Hedgehog signalling via the plasma membrane potential.

First Authors Stephanie Spannl
Authors Stephanie Spannl, Tomasz Buhl, Ioannis Nellas, Salma A Zeidan, K Venkatesan Iyer, Helena Khaliullina, Carsten Schultz, André Nadler, Natalie Dye, Suzanne Eaton
Corresponding Authors Stephanie Spannl, Natalie Dye
Last Authors Suzanne Eaton
Journal Name The EMBO journal (EMBO J)
Volume 39
Issue 21
Article Number e101767
PubMed ID 33021744
WebOfScience Link WOS:000575215200001
Open Access true
Print Publication Date 2020-10-06
Online Publication Date 2020-10-06
Abstract Changes in cell metabolism and plasma membrane potential have been linked to shifts between tissue growth and differentiation, and to developmental patterning. How such changes mediate these effects is poorly understood. Here, we use the developing wing of Drosophila to investigate the interplay between cell metabolism and a key developmental regulator-the Hedgehog (Hh) signalling pathway. We show that reducing glycolysis both lowers steady-state levels of ATP and stabilizes Smoothened (Smo), the 7-pass transmembrane protein that transduces the Hh signal. As a result, the transcription factor Cubitus interruptus accumulates in its full-length, transcription activating form. We show that glycolysis is required to maintain the plasma membrane potential and that plasma membrane depolarization blocks cellular uptake of N-acylethanolamides-lipoprotein-borne Hh pathway inhibitors required for Smo destabilization. Similarly, pharmacological inhibition of glycolysis in mammalian cells induces ciliary translocation of Smo-a key step in pathway activation-in the absence of Hh. Thus, changes in cell metabolism alter Hh signalling through their effects on plasma membrane potential.
Cover Image
Affiliated With Eaton, Nadler, Postdoc first author, Postdocs
Selected By
Acknowledged Services Scientific Computing Facility, Light Microscopy Facility
Publication Status Published
Edoc Link
Sfx Link
DOI 10.15252/embj.2019101767
Display Publisher Download Only false
Visible On MPI-CBG Website true
PDF Downloadable true
Created By thuem
Added Date 2020-10-20
Last Edited By herbst
Last Edited Date 2020-11-25 09:10:06.135
Library ID 7815
Document ID
Entry Complete true
eDoc Compliant true
Include in Edoc Report true
In Pure
Ready for eDoc Export
Author Affiliations Complete false