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A bacterial second messenger cyclic di-GMP triggers cell cycle progression
講演者：尾崎省吾 博士 所属：スイス・バーゼル大開催日：2014-11-14 17:00
終了日：2014-11-14 18:00
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講演者：尾崎省吾博士（学振海外特別研究員）
細菌の増殖制御機構の研究で顕著な業績をもつスイス・バーゼル大・ Jenal 教授の下で行なった研究です。
日時：１１月１４日（金）午後５時から６時まで
場所：薬学部第２講義室
A bacterial second messenger cyclic di-GMP triggers cell cycle progression
Shogo Ozaki, Christian Lori, Samuel Steiner, and Urs Jenal.
Focal area of Infection Biology, Biozentrum, University of Basel, Basel, Switzerland shogo.ozaki@unibas.ch
Cyclic nucleotides are ubiquitous signaling molecules conserved in all kingdoms of life. Cyclic nucleotides guide diverse reactions through binding to their own effector proteins. In most eubacterial species a second messenger cyclic di-GMP plays a fundamental part in cell fate decision between two distinct lifestyles. In a planktonic lifestyle cells establish a flagellar machinery to exhibit motility, thereby allowing host invasion or exploration of an optimal environment to grow.
Upon biosynthesis of cyclic di-GMP, cells enter a sessile lifestyle, with operating a different genetic program: i.e. loss of motility, attachment to the surface, secretion of various exopolysaccharides, and formation of an extracellular matrix so called biofilm. Those sessile cells live in a biofilm as a multicellular community. Because biofilms can be responsible for up to 80% of all infection diseases, elucidation of mechanisms underlying lifestyle decision has been of great importance especially in medical and pharmaceutical sciences. However, downstream components of cyclic di-GMP and the mechanical basis for cyclic di-GMP effectors largely remain unclear.
A prime model to study cyclic di-GMP pathways is nonpathogenic α-proteobacterium Caulobacter cresentus, which divides asymmetrically to generate two distinguishable progeny cells. While one sessile progeny, the stalked cell, is ready for a next round of DNA replication (S-phase), the other motile progeny, the swarmer cell (G1-phase), strictly blocks initiation of DNA replication and needs to be differentiated into the stalked cell to enter the S-phase. Here we show evidence that Caulobacter cells adopt oscillation of subcellular cyclic di-GMP levels in order to couple cell differentiation with cell proliferation. We genetically identify two distinct pathways downstream of cyclic di-GMP. Whereas one pathway dedicates to control of cell division, the other triggers initiation of DNA replication through binding to a novel cyclic di-GMP effector. Biochemical analyses reveal mechanisms for cyclic di-GMP-controlled action of this effector. As subcellular cyclic di-GMP levels peak at the G1-S phase transition, we propose cyclic di-GMP acts as a licensing factor for DNA replication and cell division in a eukaryotic cyclin-like manner. Our findings provide a novel insight into the cyclic di-GMP network as well as temporal and spatial regulation of key cell cycle events.
Publications:
Activation and polar sequestration of PopA, a c-di-GMP effector protein involved in Caulobacter crescentus cell cycle control.
Ozaki S, Schalch-Moser A, Zumthor L, Manfredi P, Ebbensgaard A, Schirmer T, Jenal U. Mol Microbiol. 2014 Nov;94(3):580-94
De- and repolarization mechanism of flagellar morphogenesis during a bacterial cell cycle.
Davis NJ, Cohen Y, Sanselicio S, Fumeaux C, Ozaki S, Luciano J, Guerrero-Ferreira RC, Wright ER, Jenal U, Viollier PH.
Genes Dev. 2013 Sep 15;27(18):2049-62.
世話人：片山 勉 （薬学研究院 分子生物薬学分野）