Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, USA.
Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
Sci Rep. 2021 Oct 26;11(1):21100. doi: 10.1038/s41598-021-00579-x.
The COPII component SEC24 mediates the recruitment of transmembrane cargos or cargo adaptors into newly forming COPII vesicles on the ER membrane. Mammalian genomes encode four Sec24 paralogs (Sec24a-d), with two subfamilies based on sequence homology (SEC24A/B and C/D), though little is known about their comparative functions and cargo-specificities. Complete deficiency for Sec24d results in very early embryonic lethality in mice (before the 8 cell stage), with later embryonic lethality (E7.5) observed in Sec24c null mice. To test the potential overlap in function between SEC24C/D, we employed dual recombinase mediated cassette exchange to generate a Sec24c allele, in which the C-terminal 90% of SEC24C has been replaced by SEC24D coding sequence. In contrast to the embryonic lethality at E7.5 of SEC24C-deficiency, Sec24c pups survive to term, though dying shortly after birth. Sec24c pups are smaller in size, but exhibit no other obvious developmental abnormality by pathologic evaluation. These results suggest that tissue-specific and/or stage-specific expression of the Sec24c/d genes rather than differences in cargo export function explain the early embryonic requirements for SEC24C and SEC24D.
COPII 成分 SEC24 介导跨膜货物或货物衔接器在 ER 膜上新形成的 COPII 小泡上的募集。哺乳动物基因组编码四个 Sec24 同源物（Sec24a-d），根据序列同源性分为两个亚家族（SEC24A/B 和 C/D），尽管对它们的比较功能和货物特异性知之甚少。Sec24d 的完全缺乏导致小鼠非常早期的胚胎致死（在 8 细胞阶段之前），而 Sec24c 缺失小鼠则观察到后期的胚胎致死（E7.5）。为了测试 SEC24C/D 之间功能的潜在重叠，我们采用双重重组酶介导的盒交换生成了 Sec24c 等位基因，其中 SEC24C 的 C 末端 90%已被 SEC24D 编码序列取代。与 SEC24C 缺失时 E7.5 的胚胎致死相反，Sec24c 幼仔存活至足月，但在出生后不久死亡。Sec24c 幼仔体型较小，但通过病理评估没有其他明显的发育异常。这些结果表明，Sec24c/d 基因的组织特异性和/或阶段特异性表达而不是货物输出功能的差异解释了 SEC24C 和 SEC24D 的早期胚胎需求。
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