De- and repolarization mechanism of flagellar morphogenesis during a bacterial cell cycle.
Eukaryotic morphogenesis is seeded with the establishment and subsequent amplification of polarity cues at key times during the cell cycle, often using (cyclic) nucleotide signals. We discovered that flagellum de- and repolarization in the model prokaryote Caulobacter crescentus is precisely orchestrated through at least three spatiotemporal mechanisms integrated at TipF. We show that TipF is a cell cycle-regulated receptor for the second messenger--bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP)--that perceives and transduces this signal through the degenerate c-di-GMP phosphodiesterase (EAL) domain to nucleate polar flagellum biogenesis. Once c-di-GMP levels rise at the G1 → S transition, TipF is activated, stabilized, and polarized, enabling the recruitment of downstream effectors, including flagellar switch proteins and the PflI positioning factor, at a preselected pole harboring the TipN landmark. These c-di-GMP-dependent events are coordinated with the onset of tipF transcription in early S phase and together enable the correct establishment and robust amplification of TipF-dependent polarization early in the cell cycle. Importantly, these mechanisms also govern the timely removal of TipF at cell division coincident with the drop in c-di-GMP levels, thereby resetting the flagellar polarization state in the next cell cycle after a preprogrammed period during which motility must be suspended.
Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA;
Nicole J
NJ
Davis
Yaniv
Y
Cohen
Stefano
S
Sanselicio
Coralie
C
Fumeaux
Shogo
S
Ozaki
Jennifer
J
Luciano
Ricardo C
RC
Guerrero-Ferreira
Elizabeth R
ER
Wright
Urs
U
Jenal
Patrick H
PH
Viollier
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D016935:Caulobacter crescentus / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D016764:Cell Polarity; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism; D004789:Enzyme Activation; D005407:Flagella / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D011485:Protein Binding; D021381:Protein Transport; D016415:Sequence Alignment; D015398:Signal Transduction
D001426:Bacterial Proteins; C062025:bis(3',5')-cyclic diguanylic acid; D006152:Cyclic GMP
Caulobacter; asymmetric division; c-di-GMP; cell cycle; flagellum; morphogenesis; polarity