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Titel:Import peroxisomaler Matrixproteine über die Ustilago maydis Rezeptoren Pex5a, Pex5b und Pex7
Autor:Ast, Julia
Weitere Beteiligte: Bölker, Michael (Prof. Dr.)
Veröffentlicht:2017
URI:https://archiv.ub.uni-marburg.de/diss/z2017/0080
URN: urn:nbn:de:hebis:04-z2017-00808
DOI: https://doi.org/10.17192/z2017.0080
DDC: Biowissenschaften, Biologie
Titel(trans.):Import of peroxisomal matrix proteins by the receptors Pex5a, Pex5b and Pex7 of Ustilago maydis
Publikationsdatum:2017-09-14
Lizenz:https://creativecommons.org/licenses/by/4.0

Dokument

Schlagwörter:
Pex7, Pex7, Ustilago maydis, Peroxisom, Ustilago maydis, PTS1, import, Pex5, Ustilago, PTS2, Pex5, Import, peroxisome

Zusammenfassung:
Peroxisomen sind von einer einfachen Membran umschlossene Organellen, die in den meisten eukaryotischen Zellen vorkommen. Sie sind essentiell für den Abbau von Fettsäuren und entgiften das dabei entstehende Wasserstoffperoxid. Peroxisomen und ihr enzymatischer Inhalt passen sich an die Umgebungsbedingungen und den Lebenszyklus an. Dabei können sich diese Organellen sogar so weit spezialisieren, dass sie neue Funktionen übernehmen. Trotz ihrer Diversität ist das Importsystem, mit dem lösliche Proteine aus dem Zytosol in die Peroxisomen transportiert werden, hoch konserviert. Peroxisomale Matrixproteine werden im Zytosol translatiert und im gefalteten Zustand von einem löslichen Rezeptor in die Peroxisomen importiert. Die Erkennung erfolgt dabei über peroxisomale Targeting-Signale (PTS). Diese Signale befinden sich entweder nahe des N-terminalen Endes (PTS2) oder am C-terminalen Ende (PTS1) des Proteins und werden von dem PTS2-Rezeptor Pex7 oder dem PTS1-Rezeptor Pex5 gebunden. Im Folgenden wird das geladene Matrixprotein, das Cargo, zur peroxisomalen Membran gebracht und in die Matrix transloziert. Abschließend werden die Rezeptoren recycelt und stehen für eine neue Importrunde zur Verfügung. Der phytopathogene Basidiomycet Ustilago maydis weist zwei Pex5 und ein Pex7 auf. Der Phänotyp einer pex5b-Deletionsmutante ist prominenter als der einer pex5a-Deletion. Beide Mutanten zeigen eine reduzierte Filamentbildung, verminderte Virulenz und ein eingeschränktes Wachstum auf Fettsäuren. Im Verlauf dieser Arbeit konnte nachgewiesen werden, dass sowohl Pex5a als auch Pex5b essentiell für die Verstoffwechselung von Fettsäuren sind, während der PTS2-Rezeptor unter diesen Bedingungen nicht benötigt wird. In einer bioinformatischen Analyse konnten PTS2-Proteine identifiziert werden, wobei von vielen keine Funktion bekannt ist und einige zusätzliche Zielsteuerungssignale aufweisen. Der überwiegende Teil der peroxisomalen Matrixenzyme erreicht dieses Organell über die PTS1-Rezeptoren. Bei Lokalisationsuntersuchungen von PTS1-Proteinen fiel auf, dass diese immer im Zytosol verbleiben, wenn pex5b deletiert war. Auf einige traf das auch nach Deletion von pex5a zu, obwohl diese Proteine in Wildtyp-Zellen peroxisomale Lokalisierung zeigten. Folglich werden für den Import mancher PTS1-Proteine sowohl Pex5a als auch Pex5b benötigt. Weiterhin konnte gezeigt werden, dass Pex5a nur in Anwesenheit von Pex5b den Importzyklus durchlaufen kann und dass diese Abhängigkeit über die N-terminale Domäne (NTD) von Pex5b vermittelt wird. Die NTD von Pex5b enthält auch die Pex7-bindende Domäne und ist für den Pex7-vermittelten PTS2-Import essentiell. Zudem konnte gezeigt werden, dass die Cargo-Pex5-Interaktion nicht ausschließlich über die PTS1-Bindetasche von Pex5 vermittelt wird und so zusätzlich zwischen Cargos diskrimiert werden könnte. Da pex5a und pex5b außerdem während des Lebenszyklus von U. maydis differentiell exprimiert werden, legt dies nahe, dass Pex5a und Pex5b als Regulatoren des peroxisomalen Proteoms fungieren. Dabei könnten sie das enzymatische Repertoire der Peroxisomen an den durch die Umgebungsbedingungen bestimmten Bedarf anpassen.

Summary:
Peroxisomes are organelles surrounded by a single membrane and are near-ubiquitous to eukaryotic cells. These organelles are essential for degradation of fatty acids and detoxify the in this process produced hydrogen peroxide. Peroxisomes can adapt their enzymatic content to the environment and the life cycle. Specialised peroxisomes can adopt very specific functions and are only found in a few cell types or organisms. Despite their diversity, peroxisomes share the same import system to transport proteins from the cytosol into the peroxisomal matrix. Peroxisomal proteins are translated in the cytosol and are imported as fully folded and co-factor bound proteins and even as oligomers. The vast majority of peroxisomal proteins contain a short conserved C-terminal targeting signal (PTS1). These proteins are imported by a conserved cytosolic receptor protein, Pex5. Only a few peroxisomal proteins carry an N-terminal targeting signal (PTS2), which is recognized by the receptor protein Pex7. After transferring the matrix protein across the peroxisomal membrane, the import receptors are recycled for further rounds of import. The plant pathogenic fungus Ustilago maydis encodes two Pex5 receptors (Pex5a, Pex5b) and one Pex7 receptor. Deletion of pex5a abolished growth on oleic acid but has nearly no effect on pathogenic development. In contrast, Pex5b was found to be important not only for growth on fatty acids, but also for filament formation and virulence. While both Pex5a and Pex5b are essential for growth on oleic acid the PTS2 receptor is not requiredunder these conditions. Many PTS2 proteins found in a bioinformatic analysis are of unknown function and some of them harbour additonal targeting signals, leading to the conclusion that most matrix proteins are imported by the PTS1 receptors, especially during growth on oleic acid. Deletion of pex5b disrupted the peroxisomal targeting of all PTS1 proteins. Despite their colocalisation with a peroxisomal marker protein in wild type cells, a few were found to additionally reside in the cytosol after deletion of pex5a. Thus, the peroxisomal targeting of some PTS1 proteins depends on Pex5a as well as Pex5b. In this work it could be shown, that for import functions Pex7 depends on the presence of Pex5b. As a conclusion, Pex5b serves as co-receptor for both Pex5a and Pex7. Pex5a and Pex5b do not only interact with their cargos by binding of the PTS1. It is feasible that additional interactions may serve to discriminate between different cargos. Additionally, transcription of pex5a and pex5b is differentially regulated during the life cycle of U. maydis suggesting modulation of the peroxisomal proteome in adaption to the environment.

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