Reprogramming Cdr2-Dependent Geometry-Based Cell Size Control in Fission Yeast
Reprogramming Cdr2-Dependent Geometry-Based Cell Size Control in Fission Yeast
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DOI：
10.1016/j.cub.2018.12.017
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发表时间：
2019-01-21
期刊：
影响因子：
9.2
通讯作者：
Howard, Martin
中科院分区：
文献类型：
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作者：
Facchetti, Giuseppe;Knapp, Benjamin;Howard, Martin
即使在简单的模式生物中，细胞大小是如何确定和维持的仍然不清楚。在增殖细胞中，细胞大小通过大小调节器、加法器或计时器机制或通过一些组合来协调生长和分裂来调节[1，2]。目前，最具特征的sizer行为的例子是裂殖酵母，裂殖酵母，它进入有丝分裂在一个最小的细胞大小阈值。外周膜激酶Cdr 2定位于中质膜上的簇（节点）中，并促进有丝分裂进入[3]。在这里，我们表明，Cdr 2节点的密度，其规模与细胞的大小，是由细胞感测和控制其大小。通过分析不同宽度的细胞，我们首先发现cdr 2（+）细胞在固定的细胞表面积上分裂。然而，在CDR 2 Delta突变体中的分裂更紧密地由细胞体积指定，这表明CDR 2对于面积传感是必不可少的，并且支持更紧密地基于体积的CDR 2独立的二级筛选器机制的存在。为了研究如何CDR 2节点可能感测区域，我们推导出一个最小的数学模型，该模型将细胞质激酶Ssp 1作为CDR 2激活剂。该模型预测，Ssp 1磷酸化位点中的cdr 2突变体（cdr 2-T166 A）[4]应该形成密度记录细胞长度的节点。我们通过实验证实了这一预测，并发现薄细胞现在遵循这种新的缩放比例，以恒定的长度而不是面积划分。这项工作支持的作用，Cdr 2作为一个尺寸因子，并强调了研究尺寸控制的几何方面的重要性。
How cell size is determined and maintained remains unclear, even in simple model organisms. In proliferating cells, cell size is regulated by coordinating growth and division through sizer, adder, or timer mechanisms or through some combination [1, 2]. Currently, the best-characterized example of sizer behavior is in fission yeast, Schizosaccharomyces pombe, which enters mitosis at a minimal cell size threshold. The peripheral membrane kinase Cdr2 localizes in clusters (nodes) on the medial plasma membrane and promotes mitotic entry [3]. Here, we show that the Cdr2 nodal density, which scales with cell size, is used by the cell to sense and control its size. By analyzing cells of different widths, we first show that cdr2(+) cells divide at a fixed cell surface area. However, division in the cdr2 Delta mutant is more closely specified by cell volume, suggesting that Cdr2 is essential for area sensing and supporting the existence of a Cdr2-independent secondary sizer mechanism more closely based on volume. To investigate how Cdr2 nodes may sense area, we derive a minimal mathematical model that incorporates the cytoplasmic kinase Ssp1 as a Cdr2 activator. The model predicts that a cdr2 mutant in an Ssp1 phosphorylation site (cdr2-T166A) [4] should form nodes whose density registers cell length. We confirm this prediction experimentally and find that thin cells now follow this new scaling by dividing at constant length instead of area. This work supports the role of Cdr2 as a sizer factor and highlights the importance of studying geometrical aspects of size control.