Murine SEC24D can substitute functionally for SEC24C during embryonic development.

Autor: Adams EJ; 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.; Constellation Pharmaceuticals, Cambridge, MA, 02142, USA., Khoriaty R; Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, 48109, USA. ramikhor@umich.edu.; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA. ramikhor@umich.edu.; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA. ramikhor@umich.edu.; Univeristy of Michigan Rogel Cancer Center, Ann Arbor, MI, 48109, USA. ramikhor@umich.edu., Kiseleva A; Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, USA., Cleuren ACA; Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, USA., Tomberg K; Departement of Human Genetics, University of Michigan, Ann Arbor, MI, 48109, USA., van der Ent MA; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA., Gergics P; Departement of Human Genetics, University of Michigan, Ann Arbor, MI, 48109, USA., Tang VT; Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, USA., Zhu G; Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, USA., Hoenerhoff MJ; In Vivo Animal Core, Unit of Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA., O'Shea KS; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA., Saunders TL; Transgenic Animal Model Core, University of Michigan, Ann Arbor, MI, 48109, USA., Ginsburg D; Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, USA. ginsburg@umich.edu.; Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, 48109, USA. ginsburg@umich.edu.; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA. ginsburg@umich.edu.; Department of Pediatrics, University of Michigan, Ann Arbor, MI, 48109, USA. ginsburg@umich.edu.; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, 48109, USA. ginsburg@umich.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Oct 26; Vol. 11 (1), pp. 21100. Date of Electronic Publication: 2021 Oct 26.
DOI: 10.1038/s41598-021-00579-x
Abstrakt: 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 c-d 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 c-d/c-d pups survive to term, though dying shortly after birth. Sec24c c-d/c-d 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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