Autoamplification and Competition Drive Symmetry Breaking: Initiation of Centriole Duplication by the PLK4-STIL Network.
Autoamplification and Competition Drive Symmetry Breaking: Initiation of Centriole Duplication by the PLK4-STIL Network.
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DOI：
10.1016/j.isci.2018.10.003
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发表时间：
2018-10-26
期刊：
影响因子：
5.8
通讯作者：
Goryachev AB
中科院分区：
文献类型：
--
作者：
Leda M;Holland AJ;Goryachev AB
中心粒，中心体和纤毛的核心，复制每一个细胞周期，以确保它们的忠实遗传。为什么每个母中心粒只产生一个前中心粒仍然是一个谜。我们提出了前戊三醇起始的第一个机制生物物理模型，该模型假设激酶PLK4与其激活物-底物STIL之间的相互作用是前戊三醇起始的核心。该模型概括了从围绕母中心粒的均匀PLK4“环”到启动前中心粒组装的单个PLK4“点”的转变。这种对称性破坏需要PLK4的自催化激活和磷酸化STIL增强PLK4的中心心锚定。我们发现活性PLK4的原位降解不会破坏对称性。该模型预测，PLK4- stil复合物的瞬时PLK4活性最大值之间的竞争会破坏PLK4环的稳定性，并产生单个PLK4位点。实验观察到，PLK4和STIL的过表达导致竞争减弱，导致多余的前中心细胞逐渐增加。PLK4激酶和支架STIL构成中心粒起始网络的核心，基于PLK4活性的双正反馈打破了PLK4定位的对称性，初生PLK4活性之间的竞争最大化决定了单个前中心烯在没有竞争的情况下PLK4的原位降解不能打破这种对称性；发育生物学;在硅生物学中
Centrioles, the cores of centrosomes and cilia, duplicate every cell cycle to ensure their faithful inheritance. How only a single procentriole is produced on each mother centriole remains enigmatic. We propose the first mechanistic biophysical model for procentriole initiation which posits that interactions between kinase PLK4 and its activator-substrate STIL are central for procentriole initiation. The model recapitulates the transition from a uniform “ring” of PLK4 surrounding the mother centriole to a single PLK4 “spot” that initiates procentriole assembly. This symmetry breaking requires autocatalytic activation of PLK4 and enhanced centriolar anchoring of PLK4 by phosphorylated STIL. We find that in situ degradation of active PLK4 cannot break symmetry. The model predicts that competition between transient PLK4 activity maxima for PLK4-STIL complexes destabilizes the PLK4 ring and produces instead a single PLK4 spot. Weakening of competition by overexpression of PLK4 and STIL causes progressive addition of supernumerary procentrioles, as observed experimentally. Kinase PLK4 and scaffold STIL form the core of the centriole initiation network Dual PLK4-activity-based positive feedback breaks symmetry of the PLK4 localization Competition between nascent PLK4 activity maxima determines the single procentriole In situ degradation of PLK4 cannot break the symmetry in the absence of competition Biological Sciences; Developmental Biology; In Silico Biology
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影响因子：
3.3
作者：
Gray KM;Kaifer KA;Baillat D;Wen Y;Bonacci TR;Ebert AD;Raimer AC;Spring AM;Have ST;Glascock JJ;Gupta K;Van Duyne GD;Emanuele MJ;Lamond AI;Wagner EJ;Lorson CL;Matera AG
通讯作者：
Matera AG
影响因子：
4
作者：
Guderian, Gernot;Westendorf, Jens;Nigg, Erich A.
通讯作者：
Nigg, Erich A.
影响因子：
21.3
作者：
Habedanck, R;Stierhof, YD;Nigg, EA
通讯作者：
Nigg, EA
影响因子：
4.4
作者：
Gillespie, DT
通讯作者：
Gillespie, DT
DOI：
10.1083/jcb.201801014
发表时间：
2018-04-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Aydogan MG;Wainman A;Saurya S;Steinacker TL;Caballe A;Novak ZA;Baumbach J;Muschalik N;Raff JW
通讯作者：
Raff JW