Byrne Richard D, Veeriah Selvaraju, Applebee Christopher J, Larijani Banafshé
a Cell Biophysics Laboratory; Cancer Research UK; London Research Institute; London, UK.
Nucleus. 2014 Sep-Oct;5(5):441-8. doi: 10.4161/nucl.34422.
The fusogenic lipid diacylglycerol is essential for remodeling gamete and zygote nuclear envelopes (NE) during early embryogenesis. It is unclear whether upstream signaling molecules are likewise conserved. Here we demonstrate PLCγ and its activator SFK1, which co-operate during male pronuclear envelope formation, also promote the subsequent male and female pronuclear fusion. PLCγ and SFK1 interact directly at the fusion site leading to PLCγ activation. This is accompanied by a spatially restricted reduction of PtdIns(4,5)P2. Consequently, pronuclear fusion is blocked by PLCγ or SFK1 inhibition. These findings identify new regulators of events in the early embryo and suggest a conserved "toolkit" of fusion machinery drives successive NE fusion events during embryogenesis.
促融合脂质二酰基甘油对于早期胚胎发育过程中配子和受精卵核膜(NE)的重塑至关重要。目前尚不清楚上游信号分子是否同样保守。在这里,我们证明了在雄性原核膜形成过程中协同作用的PLCγ及其激活剂SFK1,也促进随后的雄性和雌性原核融合。PLCγ和SFK1在融合位点直接相互作用,导致PLCγ激活。这伴随着磷脂酰肌醇-4,5-二磷酸(PtdIns(4,5)P2)在空间上的受限减少。因此,原核融合被PLCγ或SFK1抑制所阻断。这些发现确定了早期胚胎事件的新调节因子,并表明一种保守的融合机制“工具包”驱动胚胎发育过程中连续的核膜融合事件。