scholarly journals Self-organization of Plk4 regulates symmetry breaking in centriole duplication

2018 ◽  
Author(s):  
Shohei Yamamoto ◽  
Daiju Kitagawa
Keyword(s):  
Symmetry Breaking ◽  
Self Assembly ◽  
Self Organization ◽  
Spatial Patterning ◽  
Centriole Duplication ◽  
Dissociation Dynamics ◽  
Mother Centriole ◽  
The Asymmetry ◽  
Single Focus ◽  
Daughter Centriole

AbstractDuring centriole duplication, a single daughter centriole is formed near the mother centriole. The mechanism that determines a single duplication site is unknown. Here, we demonstrate that intrinsic self-organization of Plk4 underlies symmetry breaking in centriole duplication. We show that in its nonphosphorylated state, Plk4 preferentially self-assembles via a disordered linker and that this self-assembly is prevented by autophosphorylation. Consistently, the dissociation dynamics of centriolar Plk4 are controlled by autophosphorylation. We further found that autophophorylated Plk4 is localized as a single focus around the mother centriole before procentriole formation, and is subsequently targeted for STIL-HsSAS6 loading. Perturbing Plk4 self-organization affects the asymmetry of centriolar Plk4 distribution and centriole duplication. We propose that the spatial patterning of Plk4 directs a single duplication site per mother centriole.

scholarly journals Autoamplification and competition drive symmetry breaking: Initiation of centriole duplication by the PLK4-STIL network

2018 ◽  
Author(s):  
Marcin Leda ◽  
Andrew J. Holland ◽  
Andrew B. Goryachev
Keyword(s):  
Symmetry Breaking ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Break Symmetry ◽  
Biophysical Model ◽  
Model Organisms ◽  
Centriole Duplication ◽  
Mother Centriole ◽  
Autocatalytic Activation

SummarySymmetry breaking, a central principle of physics, has been hailed as the driver of self-organization in biological systems in general and biogenesis of cellular organelles in particular, but the molecular mechanisms of symmetry breaking only begin to become understood. Centrioles, the structural cores of centrosomes and cilia, must duplicate every cell cycle to ensure their faithful inheritance through cellular divisions. Work in model organisms identified conserved proteins required for centriole duplication and found that altering their abundance affects centriole number. However, the biophysical principles that ensure that, under physiological conditions, only a single procentriole is produced on each mother centriole remain enigmatic. Here we propose a mechanistic biophysical model for the initiation of procentriole formation in mammalian cells. We posit that interactions between the master regulatory kinase PLK4 and its activator-substrate STIL form the basis of the procentriole initiation network. The model faithfully recapitulates the experimentally observed transition from PLK4 uniformly distributed around the mother centriole, the “ring”, to a unique PLK4 focus, the “spot”, that triggers the assembly of a new procentriole. This symmetry breaking requires a dual positive feedback based on autocatalytic activation of PLK4 and enhanced centriolar anchoring of PLK4-STIL complexes by phosphorylated STIL. We find that, contrary to previous proposals,in situdegradation of active PLK4 is insufficient to break symmetry. Instead, the model predicts that competition between transient PLK4 activity maxima for PLK4-STIL complexes explains both the instability of the PLK4 ring and formation of the unique PLK4 spot. In the model, strong competition at physiologically normal parameters robustly produces a single procentriole, while increasing overexpression of PLK4 and STIL weakens the competition and causes progressive addition of procentrioles in agreement with experimental observations.

scholarly journals A molecular mechanism for the procentriole recruitment of Ana2

2019 ◽  
Vol 219 (2) ◽  
Author(s):  
Tiffany A. McLamarrah ◽  
Sarah K. Speed ◽  
John M. Ryniawec ◽  
Daniel W. Buster ◽  
Carey J. Fagerstrom ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Kinase Activity ◽  
Outer Wall ◽  
Single Site ◽  
Structural Motif ◽  
Centriole Duplication ◽  
Short Region ◽  
N Terminus ◽  
Mother Centriole ◽  
Daughter Centriole

During centriole duplication, a preprocentriole forms at a single site on the mother centriole through a process that includes the hierarchical recruitment of a conserved set of proteins, including the Polo-like kinase 4 (Plk4), Ana2/STIL, and the cartwheel protein Sas6. Ana2/STIL is critical for procentriole assembly, and its recruitment is controlled by the kinase activity of Plk4, but how this works remains poorly understood. A structural motif called the G-box in the centriole outer wall protein Sas4 interacts with a short region in the N terminus of Ana2/STIL. Here, we show that binding of Ana2 to the Sas4 G-box enables hyperphosphorylation of the Ana2 N terminus by Plk4. Hyperphosphorylation increases the affinity of the Ana2–G-box interaction, and, consequently, promotes the accumulation of Ana2 at the procentriole to induce daughter centriole formation.

scholarly journals Autophosphorylation of Polo-like Kinase 4 and Its Role in Centriole Duplication

2010 ◽  
Vol 21 (4) ◽  
pp. 547-561 ◽  
Author(s):  
James E. Sillibourne ◽  
Frederik Tack ◽  
Nele Vloemans ◽  
An Boeckx ◽  
Sathiesan Thambirajah ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Kinase Activity ◽  
Proteasome Inhibition ◽  
Centrosome Duplication ◽  
Active Fraction ◽  
Kinase Activation ◽  
Centriole Duplication ◽  
M Phase ◽  
Mother Centriole ◽  
Daughter Centriole

Centrosome duplication occurs once every cell cycle in a strictly controlled manner. Polo-like kinase 4 (PLK4) is a key regulator of this process whose kinase activity is essential for centriole duplication. Here, we show that PLK4 autophosphorylation of serine S305 is a consequence of kinase activation and enables the active fraction to be identified in the cell. Active PLK4 is detectable on the replicating mother centriole in G1/S, with the proportion of active kinase increasing through interphase to reach a maximum in mitosis. Activation of PLK4 at the replicating daughter centriole is delayed until G2, but a level equivalent to the replicating mother centriole is achieved in M phase. Active PLK4 is regulated by the proteasome, because either proteasome inhibition or mutation of the degron motif of PLK4 results in the accumulation of S305-phosphorylated PLK4. Autophosphorylation probably plays a role in the process of centriole duplication, because mimicking S305 phosphorylation enhances the ability of overexpressed PLK4 to induce centriole amplification. Importantly, we show that S305-phosphorylated PLK4 is specifically sequestered at the centrosome contrary to the nonphosphorylated form. These data suggest that PLK4 activity is restricted to the centrosome to prevent aberrant centriole assembly and sustained kinase activity is required for centriole duplication.

scholarly journals Daughter centrioles assemble preferentially towards the nuclear envelope in Drosophila syncytial embryos

2021 ◽  
Author(s):  
Neil Henry James Cunningham ◽  
Imene Bouhlel ◽  
Paul Thomas Conduit
Keyword(s):  
Nuclear Envelope ◽  
Single Mother ◽  
S Phase ◽  
Animal Cells ◽  
Simultaneous Formation ◽  
Centriole Duplication ◽  
External Cues ◽  
Mother Centriole ◽  
Pericentriolar Material ◽  
Daughter Centriole

Centrosomes are important organisers of microtubules within animal cells. They comprise a pair of centrioles surrounded by the pericentriolar material (PCM), which nucleates and organises the microtubules. To maintain centrosome numbers, centrioles must duplicate once and only once per cell cycle. During S-phase, a single new daughter centriole is built orthogonally on one side of each radially symmetric mother centriole. Mis-regulation of duplication can result in the simultaneous formation of multiple daughter centrioles around a single mother centriole, leading to centrosome amplification, a hallmark of cancer. It remains unclear how a single duplication site is established. It also remains unknown whether this site is pre-defined or randomly positioned around the mother centriole. Here, we show that within Drosophila syncytial embryos daughter centrioles preferentially assemble on the side of the mother facing the nuclear envelope, to which the centrosomes are closely attached. This positional preference is established early during duplication and remains stable throughout daughter centriole assembly, but is lost in centrosomes forced to lose their connection to the nuclear envelope. This shows that non-centrosomal cues influence centriole duplication and raises the possibility that these external cues could help establish a single duplication site.

scholarly journals A molecular mechanism for the procentriole recruitment of Ana2

2019 ◽  
Author(s):  
Tiffany A. McLamarrah ◽  
Sarah K. Speed ◽  
Daniel W. Buster ◽  
Carey J. Fagerstrom ◽  
Brian J. Galletta ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Kinase Activity ◽  
Surface Protein ◽  
Single Site ◽  
Centriole Duplication ◽  
C Terminus ◽  
N Terminus ◽  
Mother Centriole ◽  
Centriole Assembly ◽  
Daughter Centriole

AbstractCentriole duplication begins with the assembly of a pre-procentriole at a single site on a mother centriole and proceeds with the hierarchical recruitment of a conserved set of proteins, including Polo-like kinase 4 (Plk4)/ZYG-1, Ana2/SAS-5/STIL, and the cartwheel protein Sas6. During assembly, Ana2/STIL stimulates Plk4 kinase activity, and in turn, Ana2/STIL’s C-terminus is phosphorylated, allowing it to bind and recruit Sas6. The assembly steps immediately preceding Sas6-loading appear clear, but the mechanism underlying the upstream pre-procentriole recruitment of Ana2/STIL is not. In contrast to proposed models of Ana2/STIL recruitment, we recently showed that Drosophila Ana2 targets procentrioles independent of Plk4-binding. Instead, Ana2 recruitment requires Plk4 phosphorylation of Ana2’s N-terminus, but the mechanism explaining this process is unknown. Here, we show that the amyloid-like domain of Sas4, a centriole surface protein, binds Plk4 and Ana2, and facilitates phosphorylation of Ana2’s N-terminus which increases Ana2’s affinity for Sas4. Consequently, Ana2 accumulates at the procentriole to induce daughter centriole assembly.

scholarly journals Self-replication of a quantum artificial organism driven by single-photon pulses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniel Valente
Keyword(s):  
Self Assembly ◽  
Artificial Life ◽  
Single Photon ◽  
Self Organization ◽  
Physical Systems ◽  
Self Organized ◽  
Living Organisms ◽  
A Chain ◽  
Thermodynamic Mechanism ◽  
Self Replication

AbstractImitating the transition from inanimate to living matter is a longstanding challenge. Artificial life has achieved computer programs that self-replicate, mutate, compete and evolve, but lacks self-organized hardwares akin to the self-assembly of the first living cells. Nonequilibrium thermodynamics has achieved lifelike self-organization in diverse physical systems, but has not yet met the open-ended evolution of living organisms. Here, I look for the emergence of an artificial-life code in a nonequilibrium physical system undergoing self-organization. I devise a toy model where the onset of self-replication of a quantum artificial organism (a chain of lambda systems) is owing to single-photon pulses added to a zero-temperature environment. I find that spontaneous mutations during self-replication are unavoidable in this model, due to rare but finite absorption of off-resonant photons. I also show that the replication probability is proportional to the absorbed work from the photon, thereby fulfilling a dissipative adaptation (a thermodynamic mechanism underlying lifelike self-organization). These results hint at self-replication as the scenario where dissipative adaptation (pointing towards convergence) coexists with open-ended evolution (pointing towards divergence).

scholarly journals Ferro-self-assembly: magnetic and electrochemical adaptation of a multiresponsive zwitterionic metalloamphiphile showing a shape-hysteresis effect

2021 ◽  
Vol 12 (1) ◽  
pp. 270-281
Author(s):  
Stefan Bitter ◽  
Moritz Schlötter ◽  
Markus Schilling ◽  
Marina Krumova ◽  
Sebastian Polarz ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Light Scattering ◽  
Dynamic Light Scattering ◽  
Real Time ◽  
Self Assembly ◽  
Hysteresis Effect ◽  
The Self ◽  
Self Organization ◽  
Stimuli Responsive ◽  
Optical Birefringence

The self-organization properties of a stimuli responsive amphiphile can be altered by subjecting the paramagnetic oxidized form to a magnetic field of 0.8 T and monitored in real time by coupling optical birefringence with dynamic light scattering.

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