The p24 family member p23 is required for early embryonic development
The p24 family member p23 is required for early embryonic development
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DOI：
10.1016/s0960-9822(99)00266-3
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发表时间：
2000-01-13
期刊：
影响因子：
9.2
通讯作者：
Owen, MJ
中科院分区：
文献类型：
--
作者：
Denzel, A;Otto, F;Owen, MJ
P24家族的I型完整膜蛋白，定位于内质网(ER)[1-3]、中间隔室和高尔基体，被认为是内质网货物离开内质网和运输囊泡形成的受体[4-7]，p24家族的成员在分子复合体中被发现[8，9]，并富含COPI包被的囊泡，这些囊泡参与ER和高尔基复合体之间的膜运输[1]，尽管大量表达，但几个家族成员的同时缺失似乎并不影响酵母细胞的活力和蛋白质的分泌[8]。为了更深入地了解不同p24蛋白的生理作用，我们产生了一个家族成员p23表达不足的小鼠(也称为24 Delta(1)，另一种命名见[2])。与酵母遗传学不同的是，在小鼠中，两个p23等位基因的破坏都会导致早期胚胎死亡。一个等位基因的失活不仅会导致p23本身水平的降低，还会导致其他家庭成员的水平降低。稳态蛋白水平的降低也导致高尔基体结构的变化，如扩张球囊的形成，p23表达缺陷小鼠的产生，揭示了p23在哺乳动物发育的早期阶段所起的重要和非多余的作用。它还为p24家族成员参与寡聚复合体提供了遗传学证据，并表明这些蛋白在维持早期分泌途径的完整性方面发挥了结构性作用。
The p24 family of type I integral membrane proteins, which are localised in the endoplasmic reticulum (ER) [1-3], the intermediate compartment and the Golgi apparatus, are thought to function as receptors for cargo exit from the ER and in transport vesicle formation [4-7], Members of the p24 family have been found in a molecular complex [8,9] and are enriched in COPI-coated vesicles, which are involved in membrane traffic between the ER and Golgi complex [1], Although expressed abundantly, simultaneous deletion of several family members does not appear to affect cell viability and protein secretion in yeast [8], In order to gain more insights into the physiological roles of different p24 proteins, we generated mice deficient in the expression of one family member, p23 (also called 24 delta(1), see [2] for alternative nomenclature). In contrast to yeast genetics, in mice disruption of both p23 alleles resulted in early embryonic lethality. Inactivation of one allele led not only to reduced levels of p23 itself but also to reduced levels of other family members. The reduction in steady state protein levels also induced structural changes in the Golgi apparatus, such as the formation of dilated saccules, The generation of mice deficient in p23 expression has revealed an essential and non-redundant role for p23 in the earliest stages of mammalian development. It has also provided genetic evidence for the participation of p24 family members in oligomeric complexes and indicates a structural role for these proteins in maintaining the integrity of the early secretory pathway.