| 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 |