Size regulation of multiple organelles competing for a limiting subunit pool.
Size regulation of multiple organelles competing for a limiting subunit pool.
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DOI：
10.1371/journal.pcbi.1010253
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发表时间：
2022-06
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
--
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细胞如何调节细胞内结构和细胞器的大小是一个长期存在的问题。最近的实验表明，细胞内结构的大小控制是通过耗尽细胞质中的限制亚基库来实现的。虽然限制池模型确保了细胞器到细胞的大小缩放，但它没有提供用于多个共存结构的鲁棒大小控制的机制。在这里，我们开发了一个广义的细胞内结构的大小依赖性增长的理论来证明，强大的大小控制的多个细胞内结构，竞争一个有限的亚基池，是通过一个负反馈之间的增长速度和个别结构的大小。这种设计原理捕获了从细胞骨架细丝到三维细胞器的各种亚细胞结构的尺寸维持。我们确定的反馈图案的结构尺寸调节的基础上已知的分子过程，并比较我们的理论与现有的生物组件的尺寸调节模型。此外，我们发现，结构尺寸和增长率之间的正反馈可以导致的尺寸分布和自发的尺寸选择。细胞器的大小控制是真核细胞正常生理功能的关键，但其基本的大小调节机制仍然知之甚少。通过发展细胞器大小控制的一般理论，我们表明，通过单个细胞器大小和它们的净增长率之间的负反馈，实现了细胞内结构和细胞器的鲁棒大小控制。这种设计原则不仅描述了单个细胞器的大小维持，而且还确保了由有限的亚基库构建的多个共存细胞器的大小稳定性。我们的研究结果描绘了限制池的大小缩放机制，而不是一个大小控制机制的作用，支持的想法，负反馈控制的细胞器大小通过耗尽的限制亚基池是不足以维持多个竞争细胞器的大小。在细胞器大小和生长速率之间的正反馈的情况下，我们的模型再现了细胞器大小分布的双稳态和细胞极性的自发出现等现象。
How cells regulate the size of intracellular structures and organelles is a longstanding question. Recent experiments suggest that size control of intracellular structures is achieved through the depletion of a limiting subunit pool in the cytoplasm. While the limiting pool model ensures organelle-to-cell size scaling, it does not provide a mechanism for robust size control of multiple co-existing structures. Here we develop a generalized theory for size-dependent growth of intracellular structures to demonstrate that robust size control of multiple intracellular structures, competing for a limiting subunit pool, is achieved via a negative feedback between the growth rate and the size of the individual structure. This design principle captures size maintenance of a wide variety of subcellular structures, from cytoskeletal filaments to three-dimensional organelles. We identify the feedback motifs for structure size regulation based on known molecular processes, and compare our theory to existing models of size regulation in biological assemblies. Furthermore, we show that positive feedback between structure size and growth rate can lead to bistable size distribution and spontaneous size selection. Organelle size control is essential for the proper physiological functioning of eukaryotic cells, but the underlying mechanisms of size regulation remain poorly understood. By developing a general theory for organelle size control, we show that robust size control of intracellular structures and organelles is achieved via a negative feedback between individual organelle size and their net growth rates. This design principle not only describes size maintenance of single organelles, but also ensures size stability of multiple co-existing organelles that are built from a limiting pool of subunits. Our results delineate the role of limiting pool as a size scaling mechanism rather than a size control mechanism, supporting the idea that negative feedback control of organelle size via depletion of a limiting subunit pool is not sufficient to maintain the size of multiple competing organelles. In the case of positive feedback between organelle size and growth rate, our model reproduces phenomena such as bistability in organelle size distribution and spontaneous emergence of cell polarity.
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影响因子：
64.8
作者：
Dey G;Culley S;Curran S;Schmidt U;Henriques R;Kukulski W;Baum B
通讯作者：
Baum B
影响因子：
2
作者：
Erlenkaemper, C.;Kruse, K.
通讯作者：
Kruse, K.
影响因子：
16
作者：
Andrianantoandro, Ernesto;Pollard, Thomas D.
通讯作者：
Pollard, Thomas D.
影响因子：
9.2
作者：
Conduit, Paul T.;Brunk, Kathrin;Raff, Jordan W.
通讯作者：
Raff, Jordan W.
影响因子：
9.2
作者：
Decker, Markus;Jaensch, Steffen;Hyman, Anthony A.
通讯作者：
Hyman, Anthony A.