Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
Development. 2014 Jul;141(13):2724-34. doi: 10.1242/dev.110486.
Neuroblast divisions in the nematode Caenorhabditis elegans often give rise to a larger neuron and a smaller cell that dies. We have previously identified genes that, when mutated, result in neuroblast divisions that generate daughter cells that are more equivalent in size. This effect correlates with the survival of daughter cells that would normally die. We now describe a role for the DEP domain-containing protein TOE-2 in promoting the apoptotic fate in the Q lineage. TOE-2 localized at the plasma membrane and accumulated in the cleavage furrow of the Q.a and Q.p neuroblasts, suggesting that TOE-2 might position the cleavage furrow asymmetrically to generate daughter cells of different sizes. This appears to be the case for Q.a divisions where loss of TOE-2 led to a more symmetric division and to survival of the smaller Q.a daughter. Localization of TOE-2 to the membrane is required for this asymmetry, but, surprisingly, the DEP domain is dispensable. By contrast, loss of TOE-2 led to loss of the apoptotic fate in the smaller Q.p daughter but did not affect the size asymmetry of the Q.p daughters. This function of TOE-2 required the DEP domain but not localization to the membrane. We propose that TOE-2 ensures an apoptotic fate for the small Q.a daughter by promoting asymmetry in the daughter cell sizes of the Q.a neuroblast division but by a mechanism that is independent of cell size in the Q.p division.
线虫秀丽隐杆线虫中的神经母细胞分裂通常会产生一个较大的神经元和一个较小的、会死亡的细胞。我们之前已经鉴定出一些基因，这些基因发生突变会导致神经母细胞分裂产生大小更均等的子细胞。这种效应与通常会死亡的子细胞的存活相关。现在，我们描述了 DEP 结构域蛋白 TOE-2 在促进 Q 谱系中细胞凋亡命运中的作用。TOE-2 定位于质膜上，并在 Q.a 和 Q.p 神经母细胞的分裂沟中积累，这表明 TOE-2 可能将分裂沟定位成不对称的，以产生不同大小的子细胞。在 Q.a 分裂中，情况似乎就是如此，因为缺失 TOE-2 会导致更对称的分裂和较小的 Q.a 子细胞的存活。TOE-2 定位于膜上是产生这种不对称性所必需的，但令人惊讶的是，DEP 结构域是可有可无的。相比之下，缺失 TOE-2 会导致较小的 Q.p 子细胞失去凋亡命运，但不会影响 Q.p 子细胞的大小不对称性。TOE-2 的这一功能需要 DEP 结构域，但不需要定位于膜上。我们提出，TOE-2 通过促进 Q.a 神经母细胞分裂中子细胞大小的不对称性，确保了较小的 Q.a 子细胞的凋亡命运，但这一机制与 Q.p 分裂中的细胞大小无关。
