Academic Journal
Regulated targeting of the monotopic hairpin membrane protein Erg1 requires the GET pathway
| العنوان: | Regulated targeting of the monotopic hairpin membrane protein Erg1 requires the GET pathway |
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| المؤلفون: | Farkas, Ákos, Urlaub, Henning, Bohnsack, Katherine E., Schwappach, Blanche |
| سنة النشر: | 2022 |
| المجموعة: | Georg-August-Universität Göttingen: GoeScholar |
| الوصف: | The guided entry of tail-anchored proteins (GET) pathway targets C-terminally anchored transmembrane proteins and protects cells from lipotoxicity. Here, we reveal perturbed ergosterol production in ∆get3 cells and demonstrate the sensitivity of GET pathway mutants to the sterol synthesis inhibiting drug terbinafine. Our data uncover a key enzyme of sterol synthesis, the hairpin membrane protein squalene monooxygenase (Erg1), as a non-canonical GET pathway client, thus rationalizing the lipotoxicity phenotypes of GET pathway mutants. Get3 recognizes the hairpin targeting element of Erg1 via its classical client-binding pocket. Intriguingly, we find that the GET pathway is especially important for the acute upregulation of Erg1 induced by low sterol conditions. We further identify several other proteins anchored to the endoplasmic reticulum (ER) membrane exclusively via a hairpin as putative clients of the GET pathway. Our findings emphasize the necessity of dedicated targeting pathways for high-efficiency targeting of particular clients during dynamic cellular adaptation and highlight hairpin proteins as a potential novel class of GET clients. ; Deutsche Forschungsgemeinschaft ; Germany’s Excellence Strategy ; Max Planck Foundation ; Deutsche Forschungsgemeinschaft |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0021-9525 1540-8140 |
| Relation: | SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente; SFB 1190 %7C P04: Der GET-Rezeptor als ein Eingangstor zum ER und sein Zusammenspiel mit GET bodies; SFB 1190 %7C Z02: Massenspektrometrie-basierte Proteomanalyse; EXC 2067: Multiscale Bioimaging; RG K. Bohnsack (RNA Metabolism); RG Schwappach (Membrane Protein Biogenesis); https://resolver.sub.uni-goettingen.de/purl?gro-2/108437; https://sfb1190.med.uni-goettingen.de/production/literature/publications/176; https://mbexc.uni-goettingen.de/literature/publications/488 |
| DOI: | 10.1083/jcb.202201036 |
| الاتاحة: | https://resolver.sub.uni-goettingen.de/purl?gro-2/108437 https://doi.org/10.1083/jcb.202201036 https://sfb1190.med.uni-goettingen.de/production/literature/publications/176 https://mbexc.uni-goettingen.de/literature/publications/488 |
| Rights: | CC BY 4.0 ; https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.232690D6 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00219525 15408140 |
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| DOI: | 10.1083/jcb.202201036 |