A Cdc42 GEF, Gef1, through endocytosis organizes F-BAR Cdc15 along the actomyosin ring and promotes concentric furrowing
A Cdc42 GEF, Gef1, through endocytosis organizes F-BAR Cdc15 along the actomyosin ring and promotes concentric furrowing
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DOI：
10.1242/jcs.223776
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发表时间：
2019-03
影响因子：
4
通讯作者：
Udo N. Onwubiko;P. Mlynarczyk;Bin Wei;Julius Habiyaremye;Amanda Clack;S. Abel;Maitreyi E. Das
中科院分区：
文献类型：
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作者：
Udo N. Onwubiko;P. Mlynarczyk;Bin Wei;Julius Habiyaremye;Amanda Clack;S. Abel;Maitreyi E. Das
摘要 在胞质分裂过程中，裂殖酵母协调肌动球蛋白环收缩与隔膜进入，通过不明确的机制导致同心沟槽形成。我们报道，缺乏 Cdc42 激活剂 Gef1 的粟酒裂殖酵母细胞与福明 (formin) 的激活等位基因 Cdc12 相结合，表现出非同心的皱纹。非同心的皱纹细胞显示支架 Cdc15 沿环分布不均匀。这表明，在环组装后，沿环均匀分布的 Cdc15 能够实现适当的沟槽形成。我们发现，组装后，Cdc15 以 Arp2/3 复合物依赖性方式被招募到环上，并且在激活的 cdc12 突变体中减少。在 gef1 和激活的 cdc12 突变体中，皮层内吞斑块中的 cdc15 水平升高并延长了寿命。我们假设内吞作用有助于将 Cdc15 招募到组装环中；当内吞斑块含有增加的 Cdc15 水平并且斑块缔合速率缓慢时，环上的 Cdc15 分布不均匀。基于此，我们开发了一个数学模型，可以捕获实验观察到的 Cdc15 沿环的分布。我们建议，在环上，Gef1 和内吞事件促进均匀的 Cdc15 组织，以实现适当的隔膜进入和同心沟形成。重点文章：组装的肌动球蛋白环上的 Gef1 和内吞事件促进 F-BAR 蛋白 Cdc15 沿环均匀分布，从而实现同心沟槽形成。
ABSTRACT During cytokinesis, fission yeast coordinates actomyosin ring constriction with septum ingression, resulting in concentric furrow formation by a poorly defined mechanism. We report that Schizosaccharomyces pombe cells lacking the Cdc42 activator Gef1, combined with an activated allele of the formin, Cdc12, display non-concentric furrowing. Non-concentrically furrowing cells display uneven distribution of the scaffold Cdc15 along the ring. This suggests that, after ring assembly, uniform Cdc15 distribution along the ring enables proper furrow formation. We find that, after assembly, Cdc15 is recruited to the ring in an Arp2/3 complex-dependent manner and is decreased in the activated cdc12 mutant. Cdc15 at cortical endocytic patches shows increased levels and extended lifetimes in gef1 and activated cdc12 mutants. We hypothesize endocytosis helps recruit Cdc15 to assembled rings; uneven Cdc15 distribution at the ring occurs when endocytic patches contain increased Cdc15 levels and the patch-association rate is slow. Based on this, we developed a mathematical model that captures experimentally observed Cdc15 distributions along the ring. We propose that, at the ring, Gef1 and endocytic events promote uniform Cdc15 organization to enable proper septum ingression and concentric furrow formation. Highlighted Article: Gef1 and endocytic events at the assembled actomyosin ring facilitate uniform F-BAR protein Cdc15 distribution along the ring thus enabling concentric furrow formation.