Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD, 20892, USA.
Department of Cell Biology and Histology, Medical School, University of Murcia, IMIB, 30100, Murcia, Spain.
Nat Commun. 2017 Nov 21;8(1):1643. doi: 10.1038/s41467-017-01387-6.
Degradation of maternal proteins by the ubiquitin-proteasome system (UPS) accompanies the maternal-to-zygotic transition. DPPA3/Stella/PGC7, encoded by a maternal effect gene, is present in the nucleus and cytoplasm of zygotes and has been associated with protecting the female pronucleus from TET3-mediated demethylation. We now report that cytoplasmic DPPA3 is partially cleaved by the ubiquitin-proteasome system and an N-terminus fragment remains in the cytoplasm where it associates with early and re-cycling endosomes. If DPPA3 is absent or if cleavage is prevented, multiple vesicles coalesce/aggregate and markers of lysosomes are decreased. Fertilized eggs develop poorly into blastocysts, which results in significantly decreased fecundity of Dppa3 transgenic mice. This phenocopies aspects of Lamp1/2 knockdowns and Dppa3 embryos can be partially rescued in vitro by DPPA3 and to a lesser extent by LAMP1/2. Thus, the N-terminus of DPPA3 has a significant role in cytoplasmic vesicular trafficking in addition to its previously reported nuclear function.
泛素-蛋白酶体系统（UPS）降解母体蛋白伴随着母源到合子的转变。DPPA3/Stella/PGC7 是由母源效应基因编码的，存在于合子的核和细胞质中，并与保护雌性原核免受 TET3 介导的去甲基化有关。我们现在报告细胞质 DPPA3 被泛素-蛋白酶体系统部分切割，一个 N 端片段留在细胞质中，与早期和再循环内体结合。如果 DPPA3 缺失或切割被阻止，多个囊泡融合/聚集，溶酶体标记物减少。受精卵发育成囊胚的情况较差，导致 Dppa3 转基因小鼠的繁殖力显著下降。这与 Lamp1/2 敲低的方面相似，并且 Dppa3 胚胎可以在体外部分通过 DPPA3 和在较小程度上通过 LAMP1/2 得到挽救。因此，DPPA3 的 N 端除了其先前报道的核功能外，在细胞质囊泡运输中具有重要作用。
