Cytoplasmic cleavage of DPPA3 is required for intracellular trafficking and cleavage-stage development in mice.
Cytoplasmic cleavage of DPPA3 is required for intracellular trafficking and cleavage-stage development in mice.
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DOI：
10.1038/s41467-017-01387-6
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发表时间：
2017-11-21
影响因子：
16.6
通讯作者：
Dean J
中科院分区：
文献类型：
--
作者：
Shin SW;Vogt EJ;Jimenez-Movilla M;Baibakov B;Dean J
泛素蛋白酶体系统 (UPS) 对母体蛋白质的降解伴随着母体向合子的转变。 DPPA3/Stella/PGC7 由母体效应基因编码，存在于受精卵的细胞核和细胞质中，并与保护雌性原核免受 TET3 介导的去甲基化有关。我们现在报道，细胞质 DPPA3 被泛素蛋白酶体系统部分切割，N 末端片段保留在细胞质中，与早期和再循环内体结合。如果 DPPA3 缺失或裂解被阻止，多个囊泡会合并/聚集，并且溶酶体标记物会减少。受精卵发育成囊胚的能力较差，导致Dppa3R60A转基因小鼠的生育力显着下降。这种表型方面的 Lamp1/2 敲低和 Dppa3KO 胚胎可以在体外被 DPPA31-60 部分拯救，并在较小程度上被 LAMP1/2 拯救。因此，除了先前报道的核功能外，DPPA3 的 N 末端在细胞质囊泡运输中也具有重要作用。在母体到合子的转变过程中，母体蛋白质通过泛素蛋白酶体系统（UPS）降解。在这里，作者表明，在胚胎中，母系遗传的表观遗传因子 DPPA3/Stella/PGC7 被 UPS 切割并控制细胞内运输。
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 Dppa3R60A transgenic mice. This phenocopies aspects of Lamp1/2 knockdowns and Dppa3KO embryos can be partially rescued in vitro by DPPA31–60 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. During the maternal-to-zygotic transition there is degradation of maternal proteins via the ubiquitin-proteasome system (UPS). Here, the authors show that in the embryo the maternally inherited epigenetic factor DPPA3/Stella/PGC7 is cleavage by the UPS and controls intracellular trafficking.
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影响因子：
3.4
作者：
Boersema, Paul J.;Aye, Thin Thin;Mohammed, Shabaz
通讯作者：
Mohammed, Shabaz
影响因子：
3.3
作者：
Jose M;Tollis S;Nair D;Mitteau R;Velours C;Massoni-Laporte A;Royou A;Sibarita JB;McCusker D
通讯作者：
McCusker D
影响因子：
16.8
作者：
Heider MR;Gu M;Duffy CM;Mirza AM;Marcotte LL;Walls AC;Farrall N;Hakhverdyan Z;Field MC;Rout MP;Frost A;Munson M
通讯作者：
Munson M
DOI：
10.1111/j.1600-0854.2012.01353.x
发表时间：
2012-07
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
Heider MR;Munson M
通讯作者：
Munson M
影响因子：
56.9
作者：
Bostick, Magnolia;Kim, Jong Kyong;Jacobsen, Steven E.
通讯作者：
Jacobsen, Steven E.