The trafficking protein Tmed2/p24beta(1) is required for morphogenesis of the mouse embryo and placenta.

The trafficking protein Tmed2/p24beta(1) is required for morphogenesis of the mouse embryo and placenta.
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DOI:
10.1016/j.ydbio.2010.02.019
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发表时间:
2010-05-01
影响因子:
2.7
通讯作者:
Lacy, Elizabeth
Lacy, Elizabeth
中科院分区:
生物学3区
文献类型:
--
作者:
Jerome-Majewska, Loydie A.;Achkar, Tala;Luo, Li;Lupu, Floria;Lacy, Elizabeth

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在内质网和高尔基体之间的囊泡运输期间,TMED/p24蛋白家族的成员形成异源寡聚复合物,其促进蛋白质货物识别以及囊泡出芽。此外,它们还调节彼此的表达水平。尽管分析了TMED/p24蛋白在哺乳动物细胞、酵母和C. elegans,很少有人知道这个家庭在脊椎动物胚胎发生的作用。我们报告了在一个突变小鼠系99 J中Tmed 2/p24β1的单点突变的存在,该突变系是在隐性发育异常的ENU诱变筛选中鉴定的。该突变不影响Tmed 2/ p24β1 mRNA水平,但导致TMED 2/p24β1蛋白丢失。在妊娠中期死亡之前,99 J纯合子突变胚胎表现出发育延迟、异常的喙尾伸长、随机化的心脏循环和胎盘的迷路层缺失。我们发现Tmed 2/ p24β1在99 J突变胚胎中显示形态缺陷的组织中正常表达,并且这些受影响的组织缺乏TMED 2/p24β1寡聚化伴侣TMED 7/p24γ3和TMED 10/p24δ1。我们的数据揭示了TMED 2/p24β1蛋白在小鼠胚胎和胎盘的形态发生中的需求。
During vesicular transport between the endoplasmic reticulum and the Golgi, members of the TMED/p24 protein family form hetero-oligomeric complexes that facilitate protein cargo recognition as well as vesicle budding. In addition, they regulate each other's level of expression. Despite analyses of TMED/p24 protein distribution in mammalian cells, yeast, and C. elegans, little is known about the role of this family in vertebrate embryogenesis. We report the presence of a single point mutation in Tmed2/p24β1 in a mutant mouse line, 99J, identified in an ENU mutagenesis screen for recessive developmental abnormalities. This mutation does not affect Tmed2/ p24β1 mRNA levels but results in loss of TMED2/p24β1 protein. Prior to death at midgestation, 99J homozygous mutant embryos exhibit developmental delay, abnormal rostral-caudal elongation, randomized heart looping, and absence of the labyrinth layer of the placenta. We find that Tmed2/ p24β1 is normally expressed in tissues showing morphological defects in 99J mutant embryos and that these affected tissues lack the TMED2/p24β1 oligomerization partners, TMED7/p24γ3 and TMED10/p24δ1. Our data reveal a requirement for TMED2/p24β1 protein in the morphogenesis of the mouse embryo and placenta.
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