5 results on '"Lisa Gartenmann"'
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2. Centriole growth is not limited by a finite pool of components, but is limited by the Cdk1/Cyclin-dependent phosphorylation of Ana2/STIL
- Author
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Thomas L. Steinacker, Siu-Shing Wong, Zsofia A. Novak, Saroj Saurya, Lisa Gartenmann, Eline J.H. van Houtum, Judith R. Sayers, B. Christoffer Lagerholm, and Jordan W. Raff
- Abstract
Centrioles duplicate once per cell cycle but it is unclear how daughter centrioles assemble at the right time and place and grow to the right size. Here we show that in early Drosophila embryos the cytoplasmic concentrations of the key centriole assembly proteins Asl, Plk4, Ana2, Sas-6 and Sas-4 are low, but remain constant throughout the assembly process— indicating that none of them are limiting for centriole assembly. The cytoplasmic diffusion rate of Ana2/STIL, however, increased significantly towards the end of S-phase as Cdk/Cyclin activity in the embryo increased. A mutant form of Ana2 that cannot be phosphorylated by Cdk/Cyclins did not exhibit the diffusion rate change, and allowed daughter centrioles to grow for an extended period. Thus, the Cdk/Cyclin-dependent phosphorylation of cytoplasmic Ana2 seems to reduce the efficiency of daughter centriole assembly towards the end of S-phase. This helps to ensure that daughter centrioles stop growing at the correct time, and presumably also helps to explain why centrioles cannot duplicate during mitosis when Cdk/Cyclin activity is high.
- Published
- 2022
3. Sas-6, Ana2 and Sas-4 self-organise into macromolecular structures that can be used to probe centriole/centrosome assembly
- Author
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Lisa Gartenmann, Zsofi A. Novak, Jordan W. Raff, Jennifer H. Richens, Catarina Vicente, Alan Wainman, and Boris Sieber
- Subjects
PLK4 ,0303 health sciences ,Centriole ,Cell Biology ,Biology ,Spindle apparatus ,Cell biology ,03 medical and health sciences ,0302 clinical medicine ,Microtubule ,Centrosome ,030217 neurology & neurosurgery ,Actin ,030304 developmental biology ,Pericentriolar material ,Centriole assembly - Abstract
Centriole assembly requires a small number of conserved proteins. The precise pathway of centriole assembly has been difficult to study, as the lack of any one of the core assembly proteins [Plk4, Ana2 (the homologue of mammalian STIL), Sas-6, Sas-4 (mammalian CPAP) or Asl (mammalian Cep152)] leads to the absence of centrioles. Here, we use Sas-6 and Ana2 particles (SAPs) as a new model to probe the pathway of centriole and centrosome assembly. SAPs form in Drosophila eggs or embryos when Sas-6 and Ana2 are overexpressed. SAP assembly requires Sas-4, but not Plk4, whereas Asl helps to initiate SAP assembly but is not required for SAP growth. Although not centrioles, SAPs recruit and organise many centriole and centrosome components, nucleate microtubules, organise actin structures and compete with endogenous centrosomes to form mitotic spindle poles. SAPs require Asl to efficiently recruit pericentriolar material (PCM), but Spd-2 (the homologue of mammalian Cep192) can promote some PCM assembly independently of Asl. These observations provide new insights into the pathways of centriole and centrosome assembly.
- Published
- 2020
4. An Autonomous Oscillation Times and Executes Centriole Biogenesis
- Author
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Thomas L. Steinacker, Felix Zhou, Jordan W. Raff, Mohammad Mofatteh, Saroj Saurya, Lisa Gartenmann, Alain Goriely, Mustafa G. Aydogan, Z. M. Wilmott, Zsofia A Novak, Michael A. Boemo, Siu-Shing Wong, and Alan Wainman
- Subjects
PLK4 ,Centriole ,centriole duplication ,Daughter centriole ,Cell Cycle Proteins ,Biology ,Protein Serine-Threonine Kinases ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Biological Clocks ,Negative feedback ,Animals ,Drosophila Proteins ,centriole ,Phosphorylation ,030304 developmental biology ,Centrioles ,Centrosome ,0303 health sciences ,Organelle Biogenesis ,Oscillation ,organelle sizing ,Cell Cycle ,FCS ,Cell biology ,Drosophila melanogaster ,Organelle biogenesis ,biological oscillator ,biological timing ,030217 neurology & neurosurgery ,Biogenesis - Abstract
Summary The accurate timing and execution of organelle biogenesis is crucial for cell physiology. Centriole biogenesis is regulated by Polo-like kinase 4 (Plk4) and initiates in S-phase when a daughter centriole grows from the side of a pre-existing mother. Here, we show that a Plk4 oscillation at the base of the growing centriole initiates and times centriole biogenesis to ensure that centrioles grow at the right time and to the right size. The Plk4 oscillation is normally entrained to the cell-cycle oscillator but can run autonomously of it—potentially explaining why centrioles can duplicate independently of cell-cycle progression. Mathematical modeling indicates that the Plk4 oscillation can be generated by a time-delayed negative feedback loop in which Plk4 inactivates the interaction with its centriolar receptor through multiple rounds of phosphorylation. We hypothesize that similar organelle-specific oscillations could regulate the timing and execution of organelle biogenesis more generally., Graphical Abstract, Highlights • Centriolar Plk4 levels oscillate and act as a switch for centriole biogenesis • Oscillations may be generated via an Asl/Plk4 delayed negative feedback loop • Plk4 oscillations are entrained and phase-locked by the Cdk/Cyclin oscillator (CCO) • Plk4 oscillations can drive centriole biogenesis even when the CCO is perturbed, Feedback-driven oscillations in centriolar Plk4 kinase levels—normally entrained by the cell-cycle oscillator but capable of running autonomously—trigger and time centriole biogenesis to ensure that daughter centrioles grow at the right time and to the right size.
- Published
- 2019
5. A free-running oscillator times and executes centriole biogenesis
- Author
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Thomas L. Steinacker, Jordan W. Raff, Mustafa G. Aydogan, Siu S. Wong, Saroj Saurya, Lisa Gartenmann, Alan Wainman, Felix Zhou, Michael A. Boemo, and Mohammad Mofatteh
- Subjects
PLK4 ,0303 health sciences ,03 medical and health sciences ,0302 clinical medicine ,Centriole ,Cell cycle progression ,Daughter centriole ,Organelle biogenesis ,Biology ,030217 neurology & neurosurgery ,Biogenesis ,030304 developmental biology ,Cell biology - Abstract
The accurate timing of organelle biogenesis and the precise regulation of organelle size are crucial for cell physiology. Centriole biogenesis initiates exclusively in S-phase, when a daughter centriole emerges from the side of a pre-existing mother and grows until it reaches its mother’s size. This process is regulated by Polo-like kinase 4 (Plk4), which is recruited to centrioles in oscillatory waves in flies and human cells1,2. The nature and function of Plk4 oscillations is, however, unknown. Here we discover that Plk4 forms an adaptive oscillator at the base of the growing centriole, whose function is to time and set the duration of centriole biogenesis inDrosophilaembryos. We demonstrate that the Plk4 oscillator is free-running of, but is entrained and calibrated by, the core Cdk/Cyclin cell-cycle oscillator, explaining how centrioles can duplicate independently of the cell cycle3–5. Mathematical modelling and further experiments indicate that the Plk4 oscillator is generated by a time-delayed negative-feedback loop in which Plk4 recruitment to, and dissociation from, the centriole is monitored via changes in the affinity-state of its centriolar receptor, Asterless. We postulate that such organelle-specific autonomous oscillators could regulate the timing and execution of organelle biogenesis more generally.
- Published
- 2019
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