Nuclear localization of Prickle2 is required to establish cell polarity during early mouse embryogenesis.
Nuclear localization of Prickle2 is required to establish cell polarity during early mouse embryogenesis.
复制标题
DOI：
10.1016/j.ydbio.2012.01.025
复制
发表时间：
2012-04-15
影响因子：
2.7
通讯作者：
Ueno N
中科院分区：
文献类型：
--
作者：
Tao H;Inoue K;Kiyonari H;Bassuk AG;Axelrod JD;Sasaki H;Aizawa S;Ueno N
滋养外胚层（TE）的建立表现为上皮的形成，并且依赖于许多上皮组织中常见并发挥作用的许多结构和调节成分。然而，TE 形成的机制目前尚不清楚。 Prickle1 (Pk1) 是平面细胞极性 (PCP) 途径的核心组成部分，对于原肠胚形成前的外胚层极化至关重要，但 Pk 家族成员在早期小鼠胚胎发生中的作用尚不清楚。在这里，我们发现 Pk2−/− 胚胎在 E3.0–3.5 时死亡，没有形成囊胚腔，也没有维持 TE 上皮的完整性。这些表型是由于顶端-基底（AB）极性的丧失造成的，这种极性是微管网络不对称重新分布的基础，以及压实过程中AB极性成分在每个膜上的适当积累。此外，我们发现在压实过程中，Pk2−/− 胚胎中与 GTP 结合的核 RhoA 活性形式减少。我们进一步表明，第一个细胞命运决定在 Pk2−/− 胚胎中被破坏。有趣的是，尽管之前报道过 Pk2 的细胞质功能，但从 2 细胞阶段到 16 细胞阶段左右，Pk2 定位于细胞核。抑制法尼基化可阻断 Pk2 的核定位并破坏 AB 细胞极性，表明 Pk2 法尼基化对其核定位和功能至关重要。细胞极性表型被细胞核而非细胞质 Pk2 有效拯救，这表明 Pk2 的核定位对其功能至关重要。
The establishment of trophectoderm (TE) manifests as the formation of epithelium, and is dependent on many structural and regulatory components that are commonly found and function in many epithelial tissues. However, the mechanism of TE formation is currently not well understood. Prickle1 (Pk1), a core component of the planar cell polarity (PCP) pathway, is essential for epiblast polarization before gastrulation, yet the roles of Pk family members in early mouse embryogenesis are obscure. Here we found that Pk2−/− embryos died at E3.0–3.5 without forming the blastocyst cavity and not maintained epithelial integrity of TE. These phenotypes were due to loss of the apical-basal (AB) polarity that underlies the asymmetric redistribution of microtubule networks and proper accumulation of AB polarity components on each membrane during compaction. In addition, we found GTP-bound active form of nuclear RhoA was decreased in Pk2−/− embryos during compaction. We further show that the first cell fate decision was disrupted in Pk2−/− embryos. Interestingly, Pk2 localized to the nucleus from the 2-cell to around the 16-cell stage despite its cytoplasmic function previously reported. Inhibiting farnesylation blocked Pk2’s nuclear localization and disrupted AB cell polarity, suggesting that Pk2 farnesylation is essential for its nuclear localization and function. The cell polarity phenotype was efficiently rescued by nuclear but not cytoplasmic Pk2, demonstrating the nuclear localization of Pk2 is critical for its function.
登录
查看更多内容
影响因子：
2.7
作者：
Jedrusik A;Bruce AW;Tan MH;Leong DE;Skamagki M;Yao M;Zernicka-Goetz M
通讯作者：
Zernicka-Goetz M
影响因子：
5.3
作者：
Montcouquiol, Mireille;Sans, Nathalie;Kelley, Matthew W.
通讯作者：
Kelley, Matthew W.
影响因子：
4.3
作者：
Maurer-Stroh S;Koranda M;Benetka W;Schneider G;Sirota FL;Eisenhaber F
通讯作者：
Eisenhaber F
影响因子：
10.5
作者：
Jedrusik, Agnieszka;Parfitt, David-Emlyn;Zernicka-Goetz, Magdalena
通讯作者：
Zernicka-Goetz, Magdalena
影响因子：
4.6
作者：
Carreira-Barbosa, F;Concha, ML;Tada, M
通讯作者：
Tada, M