Faculty of Biology, Center for Integrative Protein Sciences Munich (CIPSM), Ludwig-Maximilians-University Munich, Planegg-Martinsried, Germany.
Department of Cell & Developmental Biology, Division of Biosciences, University College London, London, United Kingdom.
PLoS Biol. 2022 Oct 6;20(10):e3001786. doi: 10.1371/journal.pbio.3001786. eCollection 2022 Oct.
A cell's size affects the likelihood that it will die. But how is cell size controlled in this context and how does cell size impact commitment to the cell death fate? We present evidence that the caspase CED-3 interacts with the RhoGEF ECT-2 in Caenorhabditis elegans neuroblasts that generate "unwanted" cells. We propose that this interaction promotes polar actomyosin contractility, which leads to unequal neuroblast division and the generation of a daughter cell that is below the critical "lethal" size threshold. Furthermore, we find that hyperactivation of ECT-2 RhoGEF reduces the sizes of unwanted cells. Importantly, this suppresses the "cell death abnormal" phenotype caused by the partial loss of ced-3 caspase and therefore increases the likelihood that unwanted cells die. A putative null mutation of ced-3 caspase, however, is not suppressed, which indicates that cell size affects CED-3 caspase activation and/or activity. Therefore, we have uncovered novel sequential and reciprocal interactions between the apoptosis pathway and cell size that impact a cell's commitment to the cell death fate.
细胞的大小会影响其死亡的可能性。但是，在这种情况下，细胞大小是如何被控制的，细胞大小又如何影响细胞死亡命运的决定呢？我们提出证据表明，半胱天冬酶 CED-3 与秀丽隐杆线虫神经母细胞中的 RhoGEF ECT-2 相互作用，这些神经母细胞会产生“不需要的”细胞。我们推测这种相互作用促进了极性肌动球蛋白的收缩性，导致神经母细胞的不均匀分裂，并产生一个小于临界“致死”大小阈值的子细胞。此外，我们发现 ECT-2 RhoGEF 的过度激活会减小不需要的细胞的大小。重要的是，这抑制了 ced-3 半胱天冬酶部分缺失引起的“细胞死亡异常”表型，因此增加了不需要的细胞死亡的可能性。然而，ced-3 半胱天冬酶的假定无效突变并未被抑制，这表明细胞大小会影响 CED-3 半胱天冬酶的激活和/或活性。因此，我们揭示了凋亡途径和细胞大小之间影响细胞死亡命运决定的新的连续和相互作用。
