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Défense de thèse de doctorat en sciences biologiques "Caulobacter crescentus"

A NAD-dependent glutamate dehydrogenase coordinates metabolism with cell division in Caulobacter crescentus

Catégorie : défense de thèse
Date : 07/11/2014 16:30 - 07/11/2014 18:30
Lieu : Auditoire M01, Place du Palais de Justice, Namur
Orateur(s) : François BEAUFAY
Organisateur(s) : Régis HALLEZ

Patrick VIOLLIER (Univ. Genève), Leendert HAMOEN (Univ. Amsterdam), Bernard HALLET (UCL), Patsy RENARD, présidente (UNamur), Xavier DE BOLLE, co-promoteur (UNamur), Régis HALLEZ, promoteur (UNamur)



As a key process to ensure survival, development and spreading of all livings, cell division must be coordinated with other cellular processes (e.g. chromosome replication or growth) as well as according to nutrient supplies. But how bacteria control cytokinesis in function of metabolic activity remains poorly understood. In bacteria, the earliest event of cell division is the positioning of the tubulin-like GTPase FtsZ at the future division site. There, FtsZ bound to GTP assembles into protofilaments that interact laterally with each other to form a polymeric and dynamic structure called the Z-ring. At the division site, the Z-ring serves as a scaffold for all of the cell division proteins and has been proposed to drive the constriction process. Here, we identified a NAD(H)-dependent glutamate dehydrogenase (GDH) that couples cell division with cell growth in the a–proteobacterium Caulobacter crescentus. GDH catalyzes the interconversion of glutamate into NH4+ and a-ketoglutarate, thereby linking nitrogen and Krebs cycles. We found that GdhZ (for glutamate dehydrogenase interacting with FtsZ) directly stimulates the GTPase activity of FtsZ in vitro, leading to protofilaments shrinkage, only when GdhZ was enzymatically active.  Absence of GdhZ strongly delays cytokinesis and leads to various cell division defects in C. crescentus. GdhZ co-localizes with FtsZ in late predivisional cells, and oscillates throughout the cell cycle being specifically degraded at the time at which the Z-ring is assembled at the division site.  Altogether our results support a model in which active GdhZ stimulates Z-ring disassembly in late predivisional cells, thereby allowing the release of daughter cells with sufficient nutrient supplies. The fact that GdhZ has a high Km for glutamate suggests that active GdhZ could provide a “plenty” signal to the division apparatus. Interestingly, deletion of gdhZ homolog in the facultative intracellular pathogen Brucella abortus (gdhZBa) led to cell division defects similar to the ones observed in ∆gdhZCc. Moreover, ∆gdhZBa did not replicate properly inside macrophages during infection, strongly suggesting that the catabolic activity of GdhZBa is required for a successful infection.

In addition, we found that GdhZ activity is coordinated with the cell division regulator KidO during cytokinesis. KidO is a putative oxido-reductase controlling cell division only when bound to NAD(H). We show that, in vitro, KidO inhibits lateral interactions between FtsZ-protofilaments (bundles) only in the presence of NADH but not NAD+. Interestingly GdhZ and KidO are similarly regulated along the cell cycle of C. crescentus. In vitro, addition of KidO enhances GdhZ stimulatory effect on the GTPase activity of FtsZ, which lead us to propose that GdhZ and KidO act synergistically to stimulate depolymerization of the Z-ring. In our model, KidO dissociates FtsZ bundles and GdhZ stimulates GTPase activity of newly available FtsZ protofilaments.

Altogether this work illustrates how bacteria can adjust cell cycle parameters according to nutrient availability fluctuations.

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