Publikationsserver
Regulation of dynamic front-rear cell polarity by the Frz chemosensory system in Myxococcus xanthus
Bacterial cells are spatiotemporally highly organized, with proteins localizing to distinct subcellular regions. The rod-shaped Myxococcus xanthus cells move across surfaces with defined front-rear polarity. This polarity is determined by the small Ras-like GTPase MglA that localizes to the leading...
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Beteiligte: | |
| Format: | Dissertation |
| Sprache: | Englisch |
| Veröffentlicht: |
Philipps-Universität Marburg
2023
|
| Schlagworte: | |
| Online-Zugang: | PDF-Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| Zusammenfassung: | Bacterial cells are spatiotemporally highly organized, with proteins localizing to distinct subcellular regions. The rod-shaped Myxococcus xanthus cells move across surfaces with defined front-rear polarity. This polarity is determined by the small Ras-like GTPase MglA that localizes to the leading cell pole in its GTP-bound form. The nucleotide-bound form of MglA and its localization are regulated by the remaining five proteins of the polarity module. All six
proteins of the polarity module localize asymmetrically to the cell poles. Occasionally, cells invert polarity and, in parallel, reverse their direction of movement. The Frz chemosensory system triggers the inversion of cell polarity and, therefore, cellular reversals. The two output response regulators of the Frz system, FrzX and FrzZ, localize to the lagging and leading cell poles, respectively, in their phosphorylated form, targeting the proteins of the polarity module and, thereby jointly causing an inversion of the polarity of these proteins. However, the molecular mechanism that bridges FrzX and FrzZ and the proteins of the polarity module are poorly understood.
Here, we addressed this question, focusing on FrzZ. Using a biotin-based proximity labeling approach, we identify PixA as a strong candidate for directly interacting with phosphorylated FrzZ. Epistasis analyses support that FrzZ and PixA regulate reversals in the same output branch of the Frz system, and PixA inhibits reversals. In this branch, FrzZ~P induces reversals by inhibiting PixA, thereby relieving the PixA-mediated inhibition of reversals. PixA localized weakly at the lagging pole between reversals. Strikingly, Frz signaling altered PixA localization to the pole. Genetic analyses suggest that FrzZ inhibits lagging pole localization of PixA.
During Frz signaling, FrzZ~P “pulls” PixA to the leading pole, while FrzX~P “pushes off” PixA at the lagging pole. Elevated levels of PixA resulted in increased lagging pole localization of PixA and strong reduction of reversals. Altogether, our findings support a model in which PixA
inhibits reversals at the lagging cell pole while FrzX~P and FrzZ~P, in a “push and pull” mechanism, relocate PixA from the lagging to the leading pole, thereby allowing a reversal to occur.
In proximity labelling approaches, we identified the response regulator PglH as a potential interaction partner of PixA, FrzX, and MglA. A ΔpglH mutant had a hyperreversing phenotype, suggesting that PglH is a strong candidate for also being involved in regulating leading-lagging cell polarity in M. xanthus. |
|---|---|
| DOI: | 10.17192/z2024.0098 |