Publikationsserver der Universitätsbibliothek Marburg
Titel:Die dynamische Regulation der kleinen GTPase Rac1 während des polaren Wachstums von Ustilago maydis
Autor:Frieser, Sonja Helene
Weitere Beteiligte: Bölker, Michael (Prof. Dr.)
Veröffentlicht:2011
URI:https://archiv.ub.uni-marburg.de/diss/z2012/0068
URN: urn:nbn:de:hebis:04-z2012-00680
DOI: https://doi.org/10.17192/z2012.0068
DDC:570 Biowissenschaften, Biologie
Titel (trans.):The dynamic regulation of the small GTPase Rac1 during polar growth of Ustilago maydis
Publikationsdatum:2012-02-16
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
Cdc24, Ustilago maydis, Rac1, Zellpolarität, Cla4, Filament, Rac1, Cla4, Cdc24, Guaninnucleotid-Austauschfaktoren, GTP-bindende Proteine, Cell polarity, Ustilago maydis, Ustilago

Zusammenfassung:
Die morphologische Transition von der Knospung zum filamentösen Wachstum ist ein charakteristisches Merkmal vieler pathogener Pilze. Auch der Maisbrandpilz Ustilago maydis zeigt filamentöses Wachstum während seiner sexuellen Vermehrung. Daher kann er als gutes Modellsystem zum Studium der Mechanismen dienen, die dieser morphologischen Transition zugrunde liegen. Dabei hängt das filamentöse Wachstum von dem kleinen GTP-bindenden Protein Rac1 und seinem Effektor, der p21-aktivierten Kinase Cla4 ab. Kleine GTP-bindende Proteine der Rho-Familie werden durch Guaninnukleotid Austauschfaktoren (GEFs) aktiviert und durch GTPase aktivierende Proteine inaktiviert. Guaninnukleotid Dissoziationsinhibitoren (GDIs) können die Rho-GTPasen aus der Membran extrahieren und im Zytosol zurückhalten. In dieser Arbeit wurde gezeigt, dass die durch den b Kreuzungstyp kontrollierte morphologische Transition von U. maydis zur Stimulation der Rac1-Aktivität durch den GEF Cdc24 führt. Während des polaren Wachstums rekrutiert Cdc24 Rac1 in einen durch das Gerüstprotein Bem1 koordinierten Komplex mit Cla4, der an der polar wachsenden Spitze lokalisiert. Die Komplexbildung führt zur Degradierung von Cdc24, die durch die Cla4-abhängige Phosphorylierung des GEFs induziert wird. Die Expression von stabilisierten Cdc24 Varianten interferiert mit dem filamentösen Wachstum und der Pflanzeninfektion, was auf eine bedeutende Rolle des Cdc24 Abbaus während des polaren Wachstums von U. maydis hinweist. Es kann gefolgert werden, dass die Degradierung von Cdc24 die Aktivität des Bem1/Rac1-GTP/Cla4 Komplexes auf die apikale Wachstumszone beschränkt. Diese negative Rückkopplungsregulation ist von der Fähigkeit von Rac1 abhängig, zwischen der inaktiven GDP-gebundenen Konformation und dem aktiven GTP-gebundenen Zustand zu wechseln. Aus diesem Grund wurden die distinkten Funktionen von drei Rac1-GAPs und dem GDI Rdi1 während des polaren Wachstums untersucht. Es konnte gezeigt werden, dass die GAP-katalysierte Inaktivierung des Bem1/Rac1-GTP/Cla4 Komplexes und die Internalisierung von membrangebundenem Rac1 durch Rdi1, in Zusammenarbeit mit der aktinabhängigen Endozytose, für das polare Spitzenwachstum von essentieller Bedeutung sind. Die Rho-GTPasen Rac1 und Cdc42 sind eng verwandte hoch konservierte Regulatoren des Zytoskeletts und haben in U. maydis spezifische Funktionen. In dieser Arbeit konnte gezeigt werden, dass Rac1 im Komplex mit Bem1 und Cla4 durch die Mutante Cdc42F56W, die eine hohe Affinität zu Cdc24 besitzt, substituiert werden kann. Daraus lässt sich folgern, dass während des polaren Wachstums von U. maydis allein die selektive Aktivierung durch den GEF Cdc24 bestimmt, welches Rho-Protein als zentrale GTPase des Signalmoduls fungiert.

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